Search

Objective: Tumour necrosis factor (TNF)-α is a proinflammatory marker and has been shown to affect mitochondrial function in different tissues. We investigated the effect on adipose tissue (AT) inflammation and mitochondrial respiration in patients with hidradenitis suppurativa (HS) after 12 weeks of treatment with adalimumab, a TNF-α inhibitor., Methods: We sampled blood and an AT biopsy from 13 patients with HS and 10 control subjects after an overnight fast. The patients were retested after at least 12 weeks of treatment with adalimumab (40 mg/week). We measured macrophage content and mitochondrial respiration in the AT and interleukin (IL)-1β, IL-6, IL-10, high-sensitivity C-reactive protein (hsCRP), interferon-γ, TNF-α, adiponectin and leptin in plasma. Clinical scores and Dermatology Quality of Life Index (DLQI) were assessed., Results: We found a higher anti-inflammatory macrophage content (CD206 + ) in the patient group compared with the control group, but no differences between before and after the intervention. No difference in mitochondrial respiration was observed. We observed higher plasma IL-6 and hsCRP concentrations in patients with HS compared to controls, with no differences before and after the intervention. The difference between controls and HS patients was abolished after the intervention. HS patients improved their DLQI after the intervention with no change in clinical scores., Conclusion: Treatment with adalimumab in patients with HS does not alter AT inflammation or mitochondrial respiratory capacity; however, we did see a higher content of anti-inflammatory macrophages in the patient group compared with the control group., (© 2024 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: The relationship between salivary α-amylase activity (sAAa) and susceptibility to cardiovascular disorders lacks a definitive consensus in available studies. To fill this knowledge gap, the present study endeavors to investigate this association among overweight/obese otherwise healthy Qatari adults. The study specifically categorizes participants based on their sAAa into high and low subgroups, aiming to provide a more comprehensive understanding of the potential link between sAAa levels and cardiovascular and inflammation markers in this population., Methods: Plasma samples of 264 Qatari overweight/obese (Ow/Ob) participants were used to quantify the sAAa and to profile the proteins germane to cardiovascular, cardiometabolic, metabolism, and organ damage in low sAAa (LsAAa) and high sAAa (HsAAa) subjects using the Olink technology. Comprehensive statistical tools as well as chemometric and enrichments analyses were used to identify differentially expressed proteins (DEPs) and their associated signaling pathways and cellular functions., Results: A total of ten DEPs were detected, among them five were upregulated (QPCT, LCN2, PON2, DPP7, CRKL) while five were down regulated in the LsAAa subgroup compared to the HsAAa subgroup (ARG1, CTSH, SERPINB6, OSMR, ALDH3A). Functional enrichment analysis highlighted several relevant signaling pathways and cellular functions enriched in the DEPs, including myocardial dysfunction, disorder of blood pressure, myocardial infraction, apoptosis of cardiomyocytes, hypertension, chronic inflammatory disorder, immunes-mediated inflammatory disease, inflammatory response, activation of leukocytes and activation of phagocytes., Conclusion: Our study unveils substantial alterations within numerous canonical pathways and cellular or molecular functions that bear relevance to cardiometabolic disorders among Ow/Ob Qatari adults exhibiting LsAAa and HsAAa in the plasma. A more comprehensive exploration of these proteins and their associated pathways and functions offers the prospect of elucidating the mechanistic underpinnings inherent in the documented relationship between sAAa and metabolic disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khalifa, Al-Akl and Arredouani.)

Evidence regarding the role of chronic low-grade inflammation in the progression of cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM) is currently limited. This prospective cohort study, utilising data from the UK Biobank, included 273,804 adults aged 40-69 years initially free of CMD at baseline. CMM was defined as the coexistence of two or more CMDs, such as coronary artery disease, type 2 diabetes mellitus, hypertension and stroke. The aggregated inflammation score (INFLA-score), incorporating C-reactive protein, white blood cell count, platelet count and granulocyte-to-lymphocyte ratio, quantified chronic low-grade inflammation. Absolute risks (ARs), hazard ratios (HRs) and 95% confidence intervals (CIs) assessed the association of increased INFLA-score with the risk of CMMs and CMDs. The accelerated failure time model explored the effect of INFLA-score on the time to CMM onset, and a restricted cubic spline characterised the dose-dependent relationship between INFLA-score and CMM risk. After a median follow-up of 166.37 months, 13,755 cases of CMM were identified. In quartiles with increasing INFLA-score levels, CMM ARs were 4.41%, 4.49%, 5.04% and 6.01%, respectively; HR increased by 2%, 15% and 36%, respectively, compared to the lowest quartile. The INFLA-score and CMM risk relationship was nonlinear (P for nonlinear < 0.001), exhibiting a significant risk trend change at a score of 9. For INFLA-score < 9, CMM risk increased by 1.9% for each 1-point increase; for INFLA-score ≥ 9, the risk increased by 5.9% for each 1-point increase. Additionally, a higher INFLA-score was associated with an earlier onset of CMM (P < 0.001). Compared to the first INFLA-score quartile, the AFT model revealed adjusted median times to CMM occurrence were 2.92, 6.10 and 13.19 months earlier in the second, third and fourth quartile groups, respectively. Chronic low-grade inflammation is associated with a higher risk of cardiometabolic multimorbidity and earlier onset among middle-aged and older adults. Monitoring and screening the INFLA-score in adults without CMDs may improve early prevention of CMM., (© 2024. The Author(s).)

Background and Aims: Systemic low-grade inflammation, measured by plasma high-sensitivity C-reactive protein (hsCRP) levels, is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). To date, however, it is unknown whether plasma hsCRP is associated with adverse histological plaque features., Methods: Plaques were derived during carotid endarterectomy. Patients with hsCRP levels ≥2 mg/L were evaluated for pro-inflammatory and adverse plaque characteristics, as well as future ASCVD events, and compared with patients with low hsCRP levels. Logistic and linear regression analyses in addition to subdistribution hazard ratios were conducted, adjusted for cardiovascular risk factors., Results: A total of 1096 patients were included, of which 494 (46.2 %) had hsCRP levels ≥2 mg/L. Elevated hsCRP levels 2 mg/L were independently associated with levels of plaque interleukin 6, beta coefficient of 109.8 (95 % confidence interval (CI): 33.4, 186.5; p = 0.005) pg/L, interleukin 8 levels, 194.8 (110.4, 378.2; p = 0.03) pg/L and adiponectin plaque levels, -16.8 (-30.1, -3.6; p = 0.01) μg/L, compared with plaques from patients with low hsCRP levels. Histological analysis revealed increased vessel density in high hsCRP patients, odds ratio (OR) of 1.57 (1.20, 2.09; p = 0.001), larger lipid core, 1.35 (1.02, 1.73; p = 0.04), and increased macrophage content, 1.32 (1.02, 1.73; p = 0.04). Over a 3-year follow-up period, hsCRP levels ≥2 mg/L were associated with a hazard ratio of 1.81 (1.03, 3.16; p = 0.04) for coronary artery disease event risk., Conclusions: The distinct inflammatory and histological features observed in carotid plaques among individuals with hsCRP levels ≥2 mg/L underscore the utility of plasma hsCRP as a potent identifier for patients harboring high-risk plaques., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Vascular oxidative stress and low-grade inflammation are important in the pathology of cardiovascular disorders, including hypertension. Cell culture and animal studies suggest that inorganic dietary nitrate may attenuate oxidative stress and inflammation through nitric oxide (NO), and there is a need to investigate whether this translates to humans., Aim: In this randomised, placebo-controlled crossover study, by measuring a combination of multiple blood biomarkers, we evaluated whether previously reported benefits of dietary nitrate translate to a reduced oxidative stress and an improved inflammation status in 15 men and women (age range: 56-71 years) with treated hypertension., Methods: We investigated the effects of a single ∼400 mg-dose of nitrate at 3 h post-ingestion (3H POST) and the daily consumption of 2 × ∼400 mg of nitrate over 4 weeks (4WK POST), through nitrate-rich versus nitrate-depleted (placebo) beetroot juice. Measurements included plasma nitrate and nitrite (NOx), oxidised low-density lipoprotein (oxLDL), F 2 -isoprostanes, protein carbonyls, oxidised (GSSG) and reduced glutathione (GSH); and serum high-sensitive C-reactive protein (hsCRP), chemokines, cytokines, and adhesion molecules. Flow cytometry was used to assess the relative proportion of blood monocyte subsets., Results: At 4WK POST nitrate intervention, the oxLDL/NOx ratio decreased (mainly due to increases in plasma nitrate and nitrite) and the GSH/GSSG ratio (a sensitive biomarker for alterations in the redox status) increased, compared with placebo (for both ratios P < 0.01). The relative proportion of classical (CD14 + CD16 - ) monocytes decreased at 4WK POST for placebo compared to nitrate intervention (P < 0.05). Other oxidative stress and inflammatory markers were not altered by increased nitrate intake relative to placebo., Conclusions: The data from this study point toward a subtle alteration in the redox balance toward a less pro-oxidative profile by a regular intake of inorganic nitrate from plant foods., Clinical Trial Registry Number: NCT04584372 (ClinicialTrials.gov)., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Approximately one in five adults experiences chronic pain, often in co-occurrence with depression, insomnia, anxiety, and lower self-rated health. Elevated levels of cytokines, e.g. tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10), have been identified in patients with chronic pain. Depression, insufficient sleep, poor self-rated health, and pain intensity have also been associated with inflammatory biomarkers. This study aimed to investigate the interrelationships between inflammatory biomarkers and depression, insomnia, anxiety, self-rated health, sickness behavior, and pain intensity in patients with chronic pain., Methods: Self-report questionnaires and blood samples analyzed for plasma levels of inflammatory biomarkers were collected from 80 adult patients with chronic pain. Associations between inflammatory biomarkers (TNF-α, IL-6, IL-8, IL-10, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and depression, insomnia, anxiety, self-rated health, sickness behavior, and pain intensity, were analyzed using bivariate Spearman rank correlation coefficients and regression analyses., Results: Participants were mainly women (72.5 %), with a mean age of 50.8 years, and a reported mean pain duration of 16.7 years. There were significant correlations between insomnia and CRP (r s =.26, p <.05); sex and ESR (r s =.29, p <.05); age and IL-6 (r s =.29, p <.05) and IL-8 (r s =.30, p <.05); BMI and IL-6 (r s =.50, p <.001), CRP (r s =.63, p <.001) and ESR (r s =.42, p <.001). Ratings of depression were positively and significantly related to ratings of sickness behavior and anxiety (β =.32 and β =.40, respectively), explaining 49 % of the total variance in depression ratings. Insomnia was positively and significantly related to sickness behavior (β =.37) explaining 31 % of the total variance in insomnia ratings. Inflammatory biomarkers, however, did not contribute significantly to the models., Conclusions: Participants reported high levels of symptoms, yet the associations between these ratings and the inflammatory biomarkers were either absent or weak. Also, despite high levels of self-reported sickness behavior, overall the inflammatory status remained within the normal range. Ratings of sickness behavior contributed more than inflammatory markers in explaining ratings of depression and insomnia. The present results point to the complexity of chronic pain, and the challenges of identifying biomarkers that explain symptomatology., Competing Interests: Declaration of Competing Interest No conflict., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sedentary behavior (SB) is an essential risk factor for obesity, cardiovascular disease, and type 2 diabetes. Though certain levels of physical activity (PA) may attenuate the detrimental effects of SB, the inflammatory and cardiometabolic responses involved are still not fully understood. The focus of this secondary outcome analysis was to describe how light-intensity PA snacks (LIPASs, alternate sitting and standing, walking or standing continuously) compared with uninterrupted prolonged sitting affect inflammatory and cardiometabolic risk markers. Seventeen young adults with overweight and obesity participated in this study (eight females, 23.4 ± 3.3 years, body mass index (BMI) 29.7 ± 3.8 kg/m 2 , glycated hemoglobin A1C (HbA 1c ) 5.4 ± 0.3%, body fat 31.8 ± 8.2%). Participants were randomly assigned to the following conditions which were tested during an 8 h simulated workday: uninterrupted prolonged sitting (SIT), alternate sitting and standing (SIT-STAND, 2.5 h total standing time), continuous standing (STAND), and continuous walking (1.6 km/h; WALK). Each condition also included a standardized non-relativized breakfast and lunch. Venous blood samples were obtained in a fasted state at baseline (T 0 ), 1 h after lunch (T 1 ) and 8 h after baseline (T 2 ). Inflammatory and cardiometabolic risk markers included interleukin-6 (IL-6), c-reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), visceral fat area (VFA), triglyceride-glucose (TyG) index, two lipid ratio measures, TG/HDL-C and TC/HDL-C, albumin, amylase (pancreatic), total protein, uric acid, and urea. We found significant changes in a broad range of certain inflammatory and cardiometabolic risk markers during the intervention phase for IL-6 ( p = 0.014), TG ( p = 0.012), TC ( p = 0.017), HDL-C ( p = 0.020), LDL-C ( p = 0.021), albumin ( p = 0.003), total protein ( p = 0.021), and uric acid ( p = 0.040) in favor of light-intensity walking compared with uninterrupted prolonged sitting, alternate sitting and standing, and continuous standing. We found no significant changes in CRP ( p = 0.529), creatinine ( p = 0.199), TyG ( p = 0.331), and the lipid ratios TG/HDL-C ( p = 0.793) and TC/HDL-C ( p = 0.221) in response to the PA snack. During a simulated 8 h work environment replacement and interruption of prolonged sitting with light-intensity walking, significant positive effects on certain inflammatory and cardiometabolic risk markers were found in young adults with overweight and obesity.

Low-grade inflammation (LGI) mainly acted as the mediator of the association of obesity and inflammatory diet with numerous chronic diseases, including neuropsychiatric diseases. However, the evidence about the effect of LGI on brain structure is limited but important, especially in the context of accelerating aging. This study was then designed to close the gap, and we leveraged a total of 37,699 participants from the UK Biobank and utilized inflammation score (INFLA-score) to measure LGI. We built the longitudinal relationships of INFLA-score with brain imaging phenotypes using multiple linear regression models. We further analyzed the interactive effects of specific covariates. The results showed high level inflammation reduced the volumes of the subcortex and cortex, especially the globus pallidus (β [95% confidence interval] = -0.062 [-0.083, -0.041]), thalamus (-0.053 [-0.073, -0.033]), insula (-0.052 [-0.072, -0.032]), superior temporal gyrus (-0.049 [-0.069, -0.028]), lateral orbitofrontal cortex (-0.047 [-0.068, -0.027]), and others. Most significant effects were observed among urban residents. Furthermore, males and individuals with physical frailty were susceptive to the associations. The study provided potential insights into pathological changes during disease progression and might aid in the development of preventive and control targets in an age-friendly city to promote great health and well-being for sustainable development goals.

Objective: Walking pace is associated with risks of major chronic diseases including cancer, cardiovascular disease (CVD) and diabetes mellitus type 2 (T2DM) in the general population. However, whether increasing walking pace could reduce risks of major chronic diseases in individuals with hypertension remains to be explored, and the underlying mechanism potentially mediated by low-grade inflammation is also unclear., Methods: A total of 160,470 participants with hypertension were included based on the UK Biobank. The relationships of the walking pace and low-grade inflammation with risks of major chronic diseases in individuals with hypertension were assessed by the Cox proportional hazards model. Mediation analyses were performed to investigate the contribution of low-grade inflammation to the association between walking pace and risks of major chronic diseases., Results: Individuals with hypertension at the brisk walking pace had decreased risks of overall cancer and site-specific cancers (liver, lung, and endometrial cancers), all CVD events (angina, atrial fibrillation, heart failure, myocardial infarction, peripheral vascular disease and stroke), and T2DM (hazard ratios: 0.42-0.91). Increasing low-grade inflammation was associated with higher risks of aforementioned diseases except liver cancer and atrial fibrillation. Furthermore, low-grade inflammation partially mediated associations of the walking pace with risks of lung cancer, T2DM, and all CVD events (except atrial fibrillation), with mediation proportion of 2.0%-9.8%., Conclusions: Brisk walking pace was linked to reduced risks of major chronic diseases in individuals with hypertension, partially mediated by low-grade inflammation. Improving walking pace may be beneficial for health in individuals with hypertension., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase of COVID-19. Characterized by a myriad of symptoms across different organ systems, LC presents significant diagnostic and management challenges. Central to the disorder is the role of low-grade inflammation, a non-classical inflammatory response that contributes to the chronicity and diversity of symptoms observed. This review explores the pathophysiological underpinnings of LC, emphasizing the importance of low-grade inflammation as a core component. By delineating the pathogenetic relationships and clinical manifestations of LC, this article highlights the necessity for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding of LC but also inform the development of therapeutic strategies that could be applicable to other chronic conditions with similar pathophysiological features.

The prolonged consumption of a high-fat diet (HFD) leads to abnormal growth of the visceral adipose tissue (VAT), increased macrophage infiltration, and altered secretion of biologically active molecules. This is considered as a precondition for the development of obesity, inflammation, and obesity-related disorders. Therefore, we studied HFD-induced changes in the tissue levels of the inflammatory markers C-reactive protein, serum amyloid-A, and interleukin-4 in healthy male Wistar rats. The animals were first divided at random into two groups subjected to either a standard or a high-fat diet. The initial effect of the diet was evaluated after fourteen weeks. In order to study the diet duration effect, the standard diet was given to twelve animals from the HFD group, while the remaining continued with the HFD for an additional four weeks. Our results showed that the HFD barely affected body mass index, conicity, relative fat mass, and Lee indices, whereas it provoked adipocyte hypertrophy and gradually increased the levels of both the pro- and anti-inflammatory markers. The switch from the high-fat to the standard diet resulted in the comparatively fast restoration of the baseline levels of the studied molecules. Although, the prolonged consumption of an HFD causes adipocyte hypertrophy in healthy male animals, the inflammatory process in VAT is well-coordinated, time-dependent, and reversible.

Background: Emerging evidence has linked elevated resting heart rate (RHR) with poor cognitive function in older adults, but the mechanisms underlying their association are poorly understood., Methods: This population-based cross-sectional study included 4510 dementia-free participants (age ≥ 65 years; 56.9% females; 38.3% no formal education) in the baseline examination of the Multidomain Interventions to Delay Dementia and Disability in Rural China study. Of these, 1,386 had data on serum proinflammatory cytokines and adhesion molecules. RHR was measured using 12-lead electrocardiograph. We used the Mini-Mental State Examination (MMSE) and a neuropsychological test battery to assess cognitive function. Data were analyzed using the general linear and restricted cubic splines models., Results: People with high RHR were more likely to have cardiometabolic diseases and worse cognitive function (p < 0.05). There was an inverted J-shaped association of RHR with MMSE and attention scores. Having RHR ≥ 80 bpm (vs. 60-69 bpm) was significantly associated with the multivariable-adjusted β coefficients of - 0.58 [95% confidence interval (CI), - 1.00, - 0.16] for MMSE score and - 0.08 (- 0.15, - 0.01) for attention score. In the serum biomarker subsample, RHR was linearly associated with serum interleukin-6 (IL-6) (β coefficient = 0.19; 95%CI 0.14, 0.24), IL-8 (0.08; 0.02, 0.13), IL-10 (0.09; 0.04, 0.15), tumor necrosis factor-α (0.06; 0.01, 0.11), monocyte chemotactic protein-1 (0.09; 0.04, 0.15), intercellular adhesion molecule-1 (0.16; 0.11, 0.22), and vascular cell adhesion molecule-1 (0.11; 0.06, 0.16)., Conclusions: There is an inverted J-shaped association of RHR with attention and global cognition. Poor cognitive function and high RHR may be linked through systemic low-grade inflammation and endothelial injury., (© 2023. The Author(s).)

Background and Aims: The complement system, particularly the alternative complement pathway, may contribute to vascular damage and development of cardiovascular disease (CVD). We investigated the association of factor D, the rate-limiting protease in alternative pathway activation, with adverse cardiovascular outcomes., Methods: In 2947 participants (50.6% men, 59.9 ± 8.2 years, 26.5% type 2 diabetes [T2D], oversampled) we measured markers of low-grade inflammation (LGI, composite score, in SD) and, endothelial dysfunction (ED, composite score, in SD), carotid intima-media thickness (cIMT, μm), ankle-brachial index (ABI), CVD (yes/no) and plasma concentrations of factor D (in SD). Associations were estimated using multiple linear and logistic regression, adjusting for demographic, lifestyle, and dietary factors., Results: Factor D (per SD) significantly associated with LGI (0.171 SD [0.137; 0.205]), ED (0.158 SD [0.123; 0.194]) and CVD (OR 1.15 [1.04; 1.27]) but not significantly with cIMT (-6.62 μm [-13.51; 0.27]) or ABI (-0.003 [-0.007; 0.001]). Interaction analyses show that factor D more strongly associated with ED in non-diabetes (0.237 SD [0.189; 0.285] than in T2D (0.095 SD [0.034; 0.157]), p interaction <0.05. These results were largely corroborated by additional analyses with C3 and C3a. In contrast, factor D inversely associated with cIMT in non-diabetes (-13.37 μm [-21.84; -4.90]), but not in T2D (4.49 [-7.91; 16.89]), p interaction <0.05., Conclusions: Plasma factor D is independently associated with LGI, ED, and prevalent CVD but not with ABI or cIMT. Hence, greater plasma factor D concentration in CVD may potentially induce complement activation which, in turn, might contribute to further disease progression via a process that may involve inflammation and endothelial dysfunction but was not directly related to atherosclerosis or arterial injury. The observation that, in participants without diabetes, factor D associated with worse ED but smaller cIMT warrants further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Nowadays, osteoarthritis (OA), a common, multifactorial musculoskeletal disease, is considered to have a low-grade inflammatory pathogenetic component. Lately, neuropsychiatric sequelae of the disease have gained recognition. However, a link between the peripheral inflammatory process of OA and the development of neuropsychiatric pathology is not completely understood. In this review, we provide a narrative that explores the development of neuropsychiatric disease in the presence of chronic peripheral low-grade inflammation with a focus on its signaling to the brain. We describe the development of a pro-inflammatory environment in the OA-affected joint. We discuss inflammation-signaling pathways that link the affected joint to the central nervous system, mainly using primary sensory afferents and blood circulation via circumventricular organs and cerebral endothelium. The review describes molecular and cellular changes in the brain, recognized in the presence of chronic peripheral inflammation. In addition, changes in the volume of gray matter and alterations of connectivity important for the assessment of the efficacy of treatment in OA are discussed in the given review. Finally, the narrative considers the importance of the use of neuropsychiatric diagnostic tools for a disease with an inflammatory component in the clinical setting.

Low-grade inflammation is a factor that predisposes to many obesity-related comorbidities. The immune mechanisms controlling the inflammatory response related to the secretory activity of adipocytes and its consequences for the organism are still under investigation., Methods: 84 obese adult volunteers (BMI ≥ 30 kg/m 2 ) were tested by BIA. Serum samples were collected to analyze the concentrations of interleukins IL-17A, IL-17E and IL-17F. The subjects completed the original questionnaire, the FFQ-6 food consumption frequency questionnaire and the food diary., Results: The level of IL-17E and IL-17F was positively correlated with the BMI value and the level of IL-17E increased with the content of subcutaneous fat. Its increased blood concentration was also observed in individuals who declared that they were diagnosed with atherosclerosis and/or were taking beta-blockers. Products that were related with a low level of the above-mentioned interleukins were vegetables, groats, eggs, red meat, fast-food and alcohol. The level of these interleukins was positively correlated with the frequent consumption of confectionery and breakfast cereals. Nutrients that decreased the concentrations of IL-17 isoforms were potassium, iron, vitamins B6 and C, and folic acid., Conclusions: Both IL-17E and IL-17F may be closely related to the intensity of low-grade inflammation and be biomarkers of cardiovascular disease risk. Food products or the nutrients they contain may affect the levels of the above-mentioned interleukins as well as IL-17A.

Background: Chronic low-grade inflammation has been associated with high risk of several chronic diseases such as cardiovascular diseases, diabetes, depression, and dementia. As low-grade inflammation could be present long before the apparition of the disease, identifying modifiable risk factors could allow to act upstream. Psychosocial stressors at work have been suggested as modifiable risk factors of low-grade inflammation, but few longitudinal studies have evaluated the association between these stressors and inflammatory biomarkers, such as C-reactive protein (CRP) and interleukin-6 (IL-6)., Objective: This longitudinal study evaluate the associations between exposure to psychosocial stressors at work and CRP and IL-6, separately and combined into an inflammatory index., Methods: Data came from a cohort of 9188 white-collar workers recruited in 1991-1993 (T1) and followed-up after 8 (T2, 1999-2000) and 24 (T3, 2015-2018) years. Participants included in this study were randomly selected at T3 for serum biomarkers studies (n = 2557). CRP and IL-6 were measured using standardized protocols. Psychosocial stressors at work were assessed at T2 according to recognized models: Karasek's Demand-Control-Support model and Siegrist's Effort-Reward Imbalance (ERI) model, using validated questionnaires. High job strain was defined by an exposure to high psychological demand combined with low job control, and iso-strain was defined by an exposure to high job strain combined with low social support at work. ERI was defined by an imbalance between psychological demand and social, economic, and organizational reward. Several covariates were considered including sociodemographic, anthropometric, and lifestyle characteristics, and comorbidities. Prevalence ratios (PRs) and 95% confidence interval (CI) for the highest quartile of CRP, IL-6 and inflammatory index at T3 according to psychosocial stressors at work measured at T2 were calculated using generalized estimating equations. Multiple imputation and inverse probability of censoring weighting were done., Results: In men, an association was observed between exposure to iso-strain and the inflammatory index (PR of 1.42 (95% CI: 1.06;1.90)), mainly among men aged less than 65 years (PR of 2.00 (95% CI: 1.37;2.92)). In this same age group, associations with inflammatory biomarkers were also observed among men with exposure to ERI, and among women with exposure to low reward at work or moderate social support at work., Conclusion: These results suggest that psychosocial stressors at work may increase low-grade inflammation. However, further studies are needed to corroborate these results and to clarify the potential differences between men and women. As these stressors are frequent and modifiable, their reduction is important for public health and could play a role in the primary prevention of chronic diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Melatonin, the hormone of circadian rhythm regulation, is involved in the modulation of mitochondrial activity through its antioxidant and anti-inflammatory properties. Alteration of circadian rhythms such as sleep is related to obesity and metabolic pathogenesis in adulthood, but studies during childhood are scarce. The present study investigated the association of melatonin with metabolic and inflammatory markers in children with ( n = 113) and without obesity ( n = 117). Melatonin was measured in saliva four and two hours before bedtime, and after one hour of sleep. Cardiometabolic factors, high sensitivity C-reactive protein, immune markers (monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, tumor necrosis α and interferon-γ), leptin and ghrelin were determined. Sleep duration was recorded by a questionnaire. The melatonin level at 1 h after sleep was found to be increased more than twofold in children with obesity (90.16 (57.16-129.16) pg/mL) compared to controls (29.82 (19.05-61.54) pg/mL, p < 0.001) and was related to fat mass (rho = 0.294, p < 0.001); melatonin levels at 1 h after sleep were inversely correlated with high-density lipoprotein cholesterol. Positive correlation was found with apolipoprotein B, adipokines, high sensitivity C-reactive protein, plasminogen activator inhibitor-1 and tumor necrosis factor-α. Shorter sleep duration and earlier waking times were recorded in children with obesity. In conclusion, melatonin in children with obesity appears to be involved in the global metabolic and inflammatory alteration of this condition.

Chronic (continuous, non-interrupted) hypoxia and cycling (intermittent, transient) hypoxia are two types of hypoxia occurring in malignant tumors. They are both associated with the activation of hypoxia-inducible factor-1 (HIF-1) and nuclear factor κB (NF-κB), which induce changes in gene expression. This paper discusses in detail the mechanisms of activation of these two transcription factors in chronic and cycling hypoxia and the crosstalk between both signaling pathways. In particular, it focuses on the importance of reactive oxygen species (ROS), reactive nitrogen species (RNS) together with nitric oxide synthase, acetylation of HIF-1, and the action of MAPK cascades. The paper also discusses the importance of hypoxia in the formation of chronic low-grade inflammation in cancerous tumors. Finally, we discuss the effects of cycling hypoxia on the tumor microenvironment, in particular on the expression of VEGF-A, CCL2/MCP-1, CXCL1/GRO-α, CXCL8/IL-8, and COX-2 together with PGE 2 . These factors induce angiogenesis and recruit various cells into the tumor niche, including neutrophils and monocytes which, in the tumor, are transformed into tumor-associated neutrophils (TAN) and tumor-associated macrophages (TAM) that participate in tumorigenesis.

Background: Low-grade inflammation and depressiveness have been associated with chronic pain conditions., Objective: To examine whether low-grade inflammation mediates the association between depressive symptoms and temporomandibular (TM) pain in Finnish adults based on the Health 2000/2011 Surveys (BRIF8901)., Methods: The sample comprised subjects who underwent clinical TM pain examination (pain on palpation of the masticatory muscles and temporomandibular joints) in 2000 and 2011 and responded to questions on TM pain symptoms in 2011. The serum level of hs-CRP was obtained in both years, and depressiveness was assessed using the Beck Depression Inventory-21 (BDI-21) in 2000 and BDI-13 in 2011. Four subgroups were formed based on the presence of TM pain: No pain, pain in 2000-only, pain in the 2011-only, and pain in both-years. Analyses included Rao Scott's chi-square test cross-sectionally, and multinomial logistic regression longitudinally with the level of hs-CRP and BDI-21 score in 2000 as predictors. Mediation was tested using Hayes A. Processv3.5., Results: Higher BDI-21/-13 and hs-CRP levels corresponded to higher prevalences of TM pain in both years. Longitudinally, in men, higher hs-CRP level predicted TM pain in 2000-only and TM pain in both-years. Higher BDI-21 score predicted having TM pain in 2011-only. In women, higher BDI-21 score predicted TM pain in 2000-only and having TM pain in both-years. Both BDI-21 and hs-CRP had a direct effect on TM pain outcome with no mediation detected., Conclusion: While depressiveness may increase the risk of chronic TM pain in women, the risk in men is increased by low-grade inflammation.

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions affecting the adult population. OA is no longer thought to come from a purely biomechanical origin but rather one that has been increasingly recognized to include a persistent low-grade inflammatory component. Intra-articular corticosteroid injections (IACSI) have become a widely used method for treating pain in patients with OA as an effective symptomatic treatment. However, as the disease progresses, IACSI become ineffective. FKBP51 is a regulatory protein of the glucocorticoid receptor function and have been shown to be dysregulated in several pathological scenario's including chronic inflammation. Despite of these facts, to our knowledge, there are no previous studies of the expression and possible role of FKBP51 in OA. We investigated by double and triple immunofluorescence confocal microscopy the cellular and subcellular expression of FKBP51 and its relations with inflammation factors in osteoarthritic knee joint tissues: specifically, in the tibial plateau knee cartilage, Hoffa's fat pad and suprapatellar synovial tissue of the knee. Our results show co-expression of FKBP51 with TNF-α, IL-6, CD31 and CD34 in OA chondrocytes, synovial membrane cells and adipocytes in Hoffa's fat pad. FKBP51 is also abundant in nerve fibers within the fat pad. Co-expression of FKBP51 protein with these markers may be indicative of its contribution to inflammatory processes and associated chronic pain in OA., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Most chronic modern non-transmissible diseases seem to begin as the result of low-grade inflammation extending over prolonged periods of time. The importance of diet as a source of many pro-inflammatory compounds that could create and sustain such a low-grade inflammatory state cannot be ignored, particularly since we are constantly exposed to them during the day. The focus of this review is on specific components of the diet associated with inflammation, specifically advanced glycation end products (AGEs) that form during thermal processing of food. AGEs are also generated in the body in normal physiology and are widely recognized as increased in diabetes, but many people are unaware of the potential importance of exogenous AGEs ingested in food. We review experimental models, epidemiologic data, and small clinical trials that suggest an important association between dietary intake of these compounds and development of an inflammatory and pro-oxidative state that is conducive to chronic diseases. We compare dietary intake of AGEs with other widely known dietary patterns, such as the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, as well as the Dietary Inflammation Index (DII). Finally, we delineate in detail the pathophysiological mechanisms induced by dietary AGEs, both direct (i.e., non-receptor-mediated) and indirect (receptor-mediated).

Aims: To identify fecal microbiota profiles associated with metabolic abnormalities belonging to the metabolic syndrome (MS), high count of white blood cells (WBCs) and insulin resistance (IR)., Methods: Sixty-eight young patients with obesity were stratified for percentile distribution of MS abnormalities. A MS risk score was defined as low, medium, and high MS risk. High WBCs were defined as a count ≥ 7.0 10 3 /µL; severe obesity as body mass index Z-score ≥ 2 standard deviations; IR as homeostatic assessment model algorithm of IR (HOMA) ≥ 3.7. Stool samples were analyzed by 16S rRNA-based metagenomics., Results: We found reduced bacterial richness of fecal microbiota in patients with IR and high diastolic blood pressure (BP). Distinct microbial markers were associated to high BP (Clostridium and Clostridiaceae), low high-density lipoprotein cholesterol (Lachnospiraceae, Gemellaceae, Turicibacter), and high MS risk (Coriobacteriaceae), WBCs (Bacteroides caccae, Gemellaceae), severe obesity (Lachnospiraceae), and impaired glucose tolerance (Bacteroides ovatus and Enterobacteriaceae). Conversely, taxa such as Faecalibacterium prausnitzii, Parabacterodes, Bacteroides caccae, Oscillospira, Parabacterodes distasonis, Coprococcus, and Haemophilus parainfluenzae were associated to low MS risk score, triglycerides, fasting glucose and HOMA-IR, respectively. Supervised multilevel analysis grouped clearly "variable" patients based on the MS risk., Conclusions: This was a proof-of-concept study opening the way at the identification of fecal microbiota signatures, precisely associated with cardiometabolic risk factors in young patients with obesity. These evidences led us to infer, while some gut bacteria have a detrimental role in exacerbating metabolic risk factors some others are beneficial ameliorating cardiovascular host health., (© 2021. Springer-Verlag Italia S.r.l., part of Springer Nature.)

The COVID-19 pandemic examines not only the state of actual health care but also the state of fundamental medicine in various countries. Pro-inflammatory processes extend far beyond the classical concepts of inflammation. They manifest themselves in a variety of ways, beginning with extreme physiology, then allostasis at low-grade inflammation, and finally the shockogenic phenomenon of "inflammatory systemic microcirculation". The pathogenetic core of critical situations, including COVID-19, is this phenomenon. Microcirculatory abnormalities, on the other hand, lie at the heart of a specific type of general pathological process known as systemic inflammation (SI). Systemic inflammatory response, cytokine release, cytokine storm, and thrombo-inflammatory syndrome are all terms that refer to different aspects of SI. As a result, the metabolic syndrome model does not adequately reflect the pathophysiology of persistent low-grade systemic inflammation (ChSLGI). Diseases associated with ChSLGI, on the other hand, are risk factors for a severe COVID-19 course. The review examines the role of hypoxia, metabolic dysfunction, scavenger receptors, and pattern-recognition receptors, as well as the processes of the hemophagocytic syndrome, in the systemic alteration and development of SI in COVID-19.

A device that can easily measure electrical impedance might be a helpful tool for investigating the pathophysiology of gastroesophageal reflux disease. The first aim of this study was to validate our newly developed bioelectrical admittance measurement (BAM) through in vitro experimentation. The second aim was to investigate whether evaluation of BAM by this measurement differed between patients with heartburn according to their response to proton pump inhibitor (PPI) therapy. Caco-2 cell monolayers and three-dimensional tissues were examined by BAM using a frequency response analyzer. BAM was also used to measure the impedance through cell layers. Subsequently, BAM was performed during endoscopy in 41 patients experiencing heartburn without esophageal mucosal breaks. After 2-wk administration of 20-mg rabeprazole twice daily, patient responses to PPI were classified as "good" or "poor" according to their clinical course. In each patient, histological alterations and gene expression levels of inflammation mediators and tight junction proteins were evaluated. Impedance profiles indicated that monolayer Caco-2 cells on top of eight-layered normal human dermal fibroblasts had the highest magnitude of impedance over the range of frequencies. In vivo results revealed that patients with good responses to PPI displayed significantly higher admittance. Severity of low-grade inflammation was significantly associated with esophageal wall admittance. Moreover, esophageal wall admittance may be more closely related to basal zone hyperplasia than dilatation of intercellular spaces. Thus, BAM may be able to detect abnormalities in the subepithelial layer of the esophagus. NEW & NOTEWORTHY Bioelectrical admittance measurement is a new method to evaluate esophageal mucosal permeability vertically during upper gastrointestinal endoscopy. Measurement of low-grade inflammation of the esophageal mucosa with electrical conductivity shows promise in assessing proton pump inhibitor responsiveness in patients with gastroesophageal reflux disease. As various gastrointestinal diseases are associated with changes in mucosal permeability, bioelectrical admittance measurement is expected to be clinically applied to therapeutic decision-making for these diseases in the future.

Since adipose tissue (AT) can upregulate pro-inflammatory interleukins (ILs) via storing extra lipids in obesity, obesity is considered the leading cause of chronic low-grade inflammation. These ILs can pave the way for the infiltration of immune cells into the AT, ultimately resulting in low-grade inflammation and dysregulation of adipocytes. IL-1, which is divided into two subclasses, i.e., IL-1α and IL-1β, is a critical pro-inflammatory factor. In obesity, IL-1α and IL-1β can promote insulin resistance via impairing the function of adipocytes and promoting inflammation. The current study aims to review the detailed molecular mechanisms and the roles of IL-1α and IL-1β and their antagonist, interleukin-1 receptor antagonist(IL-1Ra), in developing obesity-related inflammatory complications, i.e., type II diabetes (T2D), non-alcoholic steatohepatitis (NASH), atherosclerosis, and cognitive disorders. Besides, the current study discusses the recent advances in natural drugs, synthetic agents, and gene therapy approaches to treat obesity-related inflammatory complications via suppressing IL-1., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mesenchymal stem cells from healthy adipose tissue are adipocytes progenitors with immunosuppressive potential that are used for years in cell therapy. Whether adipose stem cells (ASC) may prevent inflammation in early obesity is not known. To address this question, we performed a kinetic study of high-fat (HF) diet induced obesity in mice to follow the immune regulating functions of adipose stem cells (ASC) isolated from the subcutaneous (SAT) and the visceral adipose tissue (VAT). Our results show that, early in obesity and before inflammation was detected, HF diet durably and differently activated ASC from SAT and VAT. Subcutaneous ASC from HF-fed mice strongly inhibited the proliferation of activated T lymphocytes, whereas visceral ASC selectively inhibited TNFα expression by macrophages and simultaneously released higher concentrations of IL6. These depot specific differences may contribute to the low-grade inflammation that develops with obesity in VAT while inflammation in SAT is delayed. The mechanisms involved differ from those already described for naïve cells activation with inflammatory cytokines and probably engaged metabolic activation. These results evidence that adipose stem cells are metabolic sensors acquiring an obesity-primed immunocompetent state in answer to depot-specific intrinsic features with overnutrition, placing these cells ahead of inflammation in the local dialog with immune cells., (© 2021 Federation of American Societies for Experimental Biology.)

Purpose: It is postulated that patients with different types of pituitary neuroendocrine tumors (PitNETs) may present a higher incidence of cancer. Factors underlying individuals becoming overweight, such as insulin resistance, hyperleptinemia, and low-grade inflammation, may play a role in the risk of differentiated thyroid carcinoma (DTC) in such patients. This study aimed to investigate the frequency of and obesity-related risk factors associated with DTC in patients with PitNETs., Methods: This cross-sectional study involved 149 patients with nonacromegalic PitNETs (AG group), 71 patients with acromegaly (ACRO group), and 156 controls (CG group). All participants underwent insulin and blood glucose measurements with the determination of the homeostatic model assessment-insulin resistance (HOMA-IR) index, leptin, and high-sensitivity C-reactive protein (hsCRP), and they also underwent thyroid ultrasound. Clinically significant nodules were biopsied for subsequent cytopathological evaluation, and participants were operated on when indicated., Results: Patients in the AG group had high levels of insulin resistance and significantly higher levels of leptin and hsCRP compared with those of patients in the ACRO group. There were no cases of DTC in the AG group; two findings, one incidental, of DTC occurred in the CG group, and three cases of DTC were present in the ACRO group. Acromegaly was associated with DTC after adjusted analysis., Conclusions: Our findings in patients with nonacromegalic PitNETs do not indicate a high risk for DTC despite the presence of metabolic and inflammatory risk factors for neoplastic events. In contrast, acromegaly promotes a greater risk of DTC.

Systemic low-grade inflammation and imbalance of gut microbiota are important risk factors promoting the progression of obesity-related metabolic disorders. This provides potential pharmacological and nutritional targets for the management of obesity and obesity-related disorders. Here, we evaluated the modulatory effects of nanosilver on obesity-related systemic low-grade inflammation and gut microbial dysbiosis. C57BL/6J mice were fed with normal diet (ND) or high-fat diet (HFD) for 6 months, with/without nanosilver supplementation in drinking water. Nanosilver administration showed little systemic toxicity and did not affect the progression of obesity but mitigated the obesity-related systemic low-grade inflammation in obese mice. Such mitigation of systemic low-grade inflammation was specifically mediated by reducing the inflammatory status of epididymal visceral white adipose tissue (eWAT). Nanosilver treatments increased the diversity of gut microbial communities and markedly recovered the relative abundance of Verrucomicrobia, Epsilonbacteraeota, Actinobacteria, and Deferribacteres, without altering the proportion of Bacteroidetes or Firmicutes. The beneficial effects of nanosilver in obese mice were in association with an increase in Akkermansia but a decrease in Parasutterella at the genus level. This study suggested a potential application of nanosilver in reducing the health risks of obesity.

The product of Aoc3 gene is known as vascular adhesion protein-1 (VAP-1), a glycoprotein contributing to leukocyte extravasation and exhibiting semicarbazide-sensitive amine oxidase activity (SSAO). Regarding the immune functions of VAP-1/SSAO, it is known that mice bearing Aoc3 gene knock-out (AOC3KO) exhibit defects in leukocyte migration similar to those of mice expressing a mutated VAP-1 lacking functional SSAO activity (knock-in, AOC3KI). However, it has not been reported whether these models differ regarding other disturbances. Thus, we further compared endocrine-metabolic phenotypes of AOC3KO and AOC3KI mice to their respective control. Special attention was paid on adiposity, glucose and lipid handling, since VAP-1/SSAO is highly expressed in adipose tissue (AT). In both mouse lines, no tissue SSAO activity was found, while Aoc3 mRNA was absent in AOC3KO only. Although food consumption was unchanged, both AOC3KO and AOC3KI mice were heavier and fatter than their respective controls. Other alterations commonly found in adipocytes from both lines were loss of benzylamine insulin-like action with unchanged insulin lipogenic responsiveness and adiponectin expression. A similar downregulation of inflammatory markers (CD45, IL6) was found in AT. Glucose handling and liver mass remained unchanged, while circulating lipid profile was distinctly altered, with increased cholesterol in AOC3KO only. These results suggest that the lack of oxidase activity found in AOC3KI is sufficient to reproduce the metabolic disturbances observed in AOC3KO mice, save those related with cholesterol transport. Modulation of SSAO activity therefore constitutes a potential target for the treatment of cardiometabolic diseases, especially obesity when complicated by low-grade inflammation.

There is a great deal of impetus for the comprehensive understanding of the complete pathological function, genetic information, and functional diversity of the gut microbiota that favors the development of dementia. It has been reported that patients with mild cognitive impairment and Alzheimer's disease present with several metabolic and immune-inflammatory alterations. The recently highlighted aspects of human health linked to cognitive decline include insulin-resistance, obesity, and chronic low-grade inflammation. Gut microbiota is known to produce neurotransmitters, such as GABA, acetylcholine, dopamine or serotonin, vitamins, intestinal toxins, and modulate nerve signaling - with emphasis on the vagus nerve. Additionally, gut dysbiosis results in impaired synthesis of signaling proteins affecting metabolic processes relevant to the development of Alzheimer's disease. Due to numerous links of gut microbiota to crucial metabolic and inflammatory pathways, attempts aimed at correcting the gut microflora composition may affect dementia pathology in a pleiotropic manner. Taking advantage of the metabolic effects of cold exposure on organisms by the introduction of whole-body cryostimulation in dementia patients could lead to alterations in gut microbiota and, therefore, decrease of an inflammatory response and insulin resistance, which remain one of the critical metabolic features of dementia. Further studies are needed in order to explore the potential application of recent findings and ways of achieving the desired goals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular diseases are patterned by race and socioeconomic status, and chronic low-grade inflammation is proposed as a key underlying mechanism. Theories for how racial and socioeconomic disadvantages foster inflammation emphasize a lifecourse approach: social disadvantages enable chronic or repeated exposure to stressors, unhealthy behaviors, and environmental risks that accumulate across the lifecourse to increase low-grade inflammation. However, single samples rarely include multiple racial and socioeconomic groups that each span a wide age range, precluding examination of this proposition. To address this issue, the current study combined seven studies that measured C-reactive protein and interleukin-6, producing a pooled sample of 1650 individuals aged 11-60 years. We examined (a) whether race and socioeconomic disparities in inflammatory biomarkers vary across the lifecourse, (b) whether adiposity operates as a pathway leading to these disparities, and (c) whether any indirect pathways through adiposity also vary across the lifecourse. Relative to White individuals, Black individuals exhibited higher, whereas Asian individuals exhibited lower, levels of inflammatory biomarkers, and adiposity accounted for these racial differences. Similarly, lower socioeconomic status was associated with higher inflammatory biomarkers via elevated adiposity. Importantly, both racial and socioeconomic disparities, as well as their pathways via adiposity, widened across the lifecourse. This pattern suggests that the impact of social disadvantages compound with age, leading to progressively larger disparities in low-grade inflammation. More broadly, these findings highlight the importance of considering age when examining health disparities and formulating conceptual models that specify how and why disparities may vary across the lifecourse., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: We investigated the impact of fish oil and/or probiotics on serum and vaginal inflammatory and metabolic proteins and their relation to the onset of gestational diabetes mellitus (GDM)., Methods: Overweight/obese pregnant women received fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo from early pregnancy until six months postpartum (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid; probiotics: Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 10 10 colony-forming units each). Serum high sensitivity C-reactive protein (hsCRP) and serum/vaginal (s/v) phosphorylated insulin-like growth factor binding-protein-1 (phIGFBP-1), IGFBP-1 and matrix metalloproteinase 8 (MMP-8) were analyzed. GDM was diagnosed according to 2 h 75 g OGTT., Results: The intervention had no impact on the change in proteins during pregnancy. Nevertheless, s-MMP-8 decreased and s-IGFBP-1 increased more in obese than in overweight women in the fish oil + probiotics group, while a decrease in s-MMP-8 was seen in obese women and an increase was seen in overweight women in the probiotics + placebo group. The late pregnancy s-phIGFBP-1 was higher in women who developed GDM in fish oil + probiotics-group compared to fish oil + placebo-group. The concentrations of s-phIGFBP-1 (635.9 ± 315.3 ng/mL vs. 753.2 ± 335.1 ng/mL, p = 0.005) and s-IGFBP-1 (3.78 ± 0.72 ng/mL vs. 3.96 ± 0.69 ng/mL, p = 0.042) were lower in early pregnancy in women who developed GDM than in women remaining healthy., Conclusions: The intervention per se had no impact on the proteins, but obesity and GDM may modify the effect. IGFBPs may affect the development of GDM.

Background and Aims: Several cross-sectional, but few prospective, studies suggest that inflammation may be involved in the development of high blood pressure. We examined markers of inflammation for their associations with blood pressure levels over a two-year period in healthy adolescents., Methods and Results: The sample comprised 406 adolescents (209 girls) aged 12-18 years in the LabMed Physical Activity Study were followed-up for 2 years. Anthropometric (weigh, height, BMI), markers of inflammation (high sensitivity C-reactive protein, complement factors C3 and C4, fibrinogen, leptin and adiponectin) and ambulatory blood pressure (BP) were collected. Socioeconomic status, pubertal development, adherence to Mediterranean diet and cardiorespiratory fitness were measured for adjustment for potential confounders. Adjusted linear regression models revealed a significant association of Leptin/Adiponectin (L/A) Ratio (baseline) with systolic BP (β = 0.120; p < 0.034) and with diastolic BP (β = 0.125; p < 0.036) at follow-up (full adjusted model). Leptin was associated with systolic BP at follow-up (β = 0.102; p < 0.038) after adjustment for systolic BP at baseline, height, pubertal stage, socioeconomic status, adherence to Mediterranean diet, cardiorespiratory fitness, however, not independently of BMI., Conclusion: L/A ratio was positively associated with systolic BP and diastolic BP even after adjusting confounding variables. Therefore, a higher misbalance between leptin and adiponectin (higher L/A ratio) early adolescence may exert a negative effect BP levels in late adolescence regardless of several confounders factors., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Background and Aims: Pediatric obesity associates with both low-grade inflammation and cardiometabolic risk on the population level. Yet on an individual patient level, overweight/obesity does not always equal increased cardiometabolic risk. In this study, we examine whether low-grade inflammation associates with cardiometabolic risk in Danish children, independent of degree of adiposity. We further assess the value of integrating multiple inflammation markers to identify children with very-high cardiometabolic risk profiles., Method and Results: We studied 2192 children and adolescents aged 6-18 years from an obesity clinic cohort and a population-based cohort, in a cross-sectional study design. Anthropometry, blood pressure, pubertal stage and body composition by dual-energy X-ray absorptiometry were assessed, and biomarkers including fasting serum high sensitivity C-reactive protein (hsCRP), white blood cells (WBC), resistin, lipid profile and glucose metabolism were measured. Adjusted correlation analysis and odds ratios were calculated. We found that, independent of degree of adiposity, having high-normal inflammation marker concentrations associated with increased cardiometabolic risk: for girls, hsCRP >0.57-9.98 mg/L (mid/upper tertile) associated with ~2-fold higher odds of dyslipidemia and hepatic steatosis (vs. lower tertile). For both sexes, WBC >7.0-12.4 10 9 /L (upper tertile) associated with 2.5-fold higher odds of insulin resistance. Lastly, children with multiple inflammation markers in the high-normal range exhibited the most severe cardiometabolic risk profile., Conclusion: Low-grade inflammation associates with cardiometabolic risk in children independent of degree of adiposity. The associations vary with sex and inflammation marker measured. Finally, integrating multiple low-grade inflammation markers identifies a very-high-risk subgroup of children with overweight/obesity and may have clinical value., Competing Interests: Declaration of Competing Interest JH received lecture fees from Novo Nordisk and is the owner of Dr Holm Ltd, which provides medical services, training and supervision. All other authors have nothing to disclose., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of the present study was to derive overall and sex-specific dietary patterns associated with inflammatory biomarkers in a general population sample from Northern Germany., Methods: The present analysis included 1158 participants (477 men, 681 women, mean age: 53.1 years; mean body mass index: 26.2 kg/m 2 ) of the Food Chain Plus (FoCus) cohort in Kiel, Germany. Participants completed a semi-quantitative food frequency questionnaire and provided blood samples. Reduced rank regression with C-reactive protein (CRP) and Interleukin 6 (IL-6) as response variables was used to derive dietary patterns. After a mean follow-up of 1.7 years, a second blood sample was obtained in a subsample of 112 individuals. Multiple regression models were used to examine the association between dietary patterns at baseline and inflammatory biomarkers at follow-up., Results: The overall pattern characterised by high intakes of soft drinks, meat, potatoes and sauce, and low intakes of other cereals (except pasta/rice), wine, nuts, seeds, vegetarian dishes, vegetable oil, and fish was positively associated with CRP (OR 2.20; 95% CI 1.12, 4.35) and IL-6 (OR 3.14; 95% CI 1.26, 7.87) at follow-up. In men, the dietary pattern was higher in soft drinks, processed meat and low in cereals and plant-based fats. In women, the pattern was characterised by soft drinks, meat, vegetables and low in other cereals, wine, nuts, and seeds. The association between sex-specific patterns with inflammatory biomarkers was weaker for CRP., Conclusion: We identified dietary patterns positively associated with established biomarkers of chronic low-grade inflammation.

Background and objectives: Periodontitis is a multifactorial chronic inflammatory infectious disease in which an infection is necessary, but not sufficient, for development of the condition. Individual susceptibility strictly linked to the immune and inflammatory response of the organism must also be present. Low-grade inflammation (LGI) is a systemic status of chronic sub-clinical production of inflammatory factors. This condition represents a risk factor for many chronic diseases including diabetes, cardiovascular disease, cerebrovascular disease, neurodegenerative disease and cancer. This scoping review aims to clarify, summarize and disseminate current knowledge on the possible link between periodontitis, LGI and systemic health. Materials and Methods: PRISMA Extension for Scoping Reviews guidelines were followed. An ad-hoc created keyword string was used to search the electronic databases of PubMed/Medline, Embase, The Cochrane Library and ClinicalTrials.gov. A hand search of specialized journals and their reference lists was also performed. Results: 14 studies that respected eligibility criteria were selected and analyzed. There is emerging evidence of strong links between periodontitis, LGI and systemic health. On the one hand, periodontitis influences the systemic status of LGI and on the other hand, the systemic production of inflammatory factors affects periodontitis with a bidirectional connection. Conclusions: LGI and the subsequent onset of a systemic inflammatory phenotype can be considered the common substrate of many chronic inflammatory diseases including periodontitis, with multiple mutual connections between them. Understanding of the biological principles and mechanisms underlying such a complex interrelationship could lead to significant improvements in the field of personalized diagnostics and therapeutic protocols., Competing Interests: The authors declare no conflict of interest.

Oxidative stress plays a key role for the development of cardiovascular, metabolic, and neurodegenerative disease. This concept has been proven by using the approach of genetic deletion of reactive oxygen and nitrogen species (RONS) producing, pro-oxidant enzymes as well as by the overexpression of RONS detoxifying, antioxidant enzymes leading to an amelioration of the severity of diseases. Vice versa, the development and progression of cardiovascular diseases is aggravated by overexpression of RONS producing enzymes as well as deletion of RONS detoxifying enzymes. We have previously identified cross talk mechanisms between different sources of RONS, which can amplify the oxidative stress-mediated damage. Here, the pathways and potential mechanisms leading to this cross talk are analyzed in detail and highlighted by selected examples from the current literature and own data including hypoxia, angiotensin II (AT-II)-induced hypertension, nitrate tolerance, aging, and others. The general concept of redox-based activation of RONS sources via "kindling radicals" and enzyme-specific "redox switches" as well as the interaction with redox-sensitive inflammatory pathways are discussed. Here, we present evidence for the existence of such cross talk mechanisms in the setting of diabetes and critically assess their contribution to the severity of diabetic complications.

Aims: Small dense low-density lipoprotein cholesterol (sdLDL-C) and remnant-like particle cholesterol (RLP-C) are the novel atherosclerotic risk factors and might be strongly associated with inflammation. The basic evidence supports that sdLDL and RLP have some different mechanisms inducing an inflammatory response. Many studies have focused on the mechanism of inflammation of sdLDL-C or RLP-C per se, with limited data on the association between sdLDL-C and RLP-C in the real-world, population-based setting. Thus, the aim of this study was to investigate the association between sdLDL-C and RLP-C with inflammation., Methods: We examined the baseline cross-sectional data of participants from the Jichi Medical School-II Cohort Study. In total, 5,305 participants (2,439 men and 2,866 women) were included in this study., Results: Of all quartiles of sdLDL-C, the fourth had the highest high-sensitivity C-reactive protein (hs-CRP) level. Once adjusted for age, sex, smoking status, homeostasis model assessment of insulin resistance, antidyslipidemic and antihyperglycemic medication use, and RLP-C, sdLDL-C was significantly and positively associated with hs-CRP (geometric mean, 95% confidence interval (CI), 0.36 mg/L (0.34-0.38 mg/L), 0.37 mg/L (0.35-0.39 mg/L), 0.40 mg/L (0.37-0.42 mg/L) versus 0.44 mg/L (0.42-0.47 mg/L), P＜0.001 for trend). After stratifying the participants into four sdLDL-C×four RLP-C categories, the group in the fourth sdLDL-C quartile and the forth RLP-C quartile had the highest hs-CRP level (geometric mean, 95% CI, 0.52 mg/L, 0.48-0.57 mg/L, interaction P=0.75)., Conclusions: SdLDL-C and RLP-C had different associations with inflammation. Our results support sdLDL-C as the potential novel factor of cardiovascular disease, independently of RLP-C.

The importance of the postprandial state has been acknowledged, since hyperglycemia and hyperlipidemia are linked with several chronic systemic low-grade inflammation conditions. Humans spend more than 16 h per day in the postprandial state and the postprandial state is acknowledged as a complex interplay between nutrients, hormones and diet-derived metabolites. The purpose of this review is to provide insight into the physiology of the postprandial inflammatory response, the role of different nutrients, the pro-inflammatory effects of metabolic endotoxemia and the anti-inflammatory effects of bile acids. Moreover, we discuss nutritional strategies that may be linked to the described pathways to modulate the inflammatory component of the postprandial response.

Cognitive dysfunction, one of the major concerns of increased life expectancy, is prevalent in patients with metabolic disorders. Added to the inflammation in the context of aging (inflammaging), low-grade chronic inflammation (metaflammation) accompanies metabolic diseases. Peripheral and central inflammation underlie metabolic syndrome - related cognitive dysfunction. The gut microbiota is increasingly recognized to be linked to both inflammaging and metaflammation in parallel to the pathophysiology of obesity, type 2 diabetes and the metabolic syndrome. Microbiota composition, diversity and diverse metabolites have been related to different metabolic features and cognitive traits. The study of different mouse models has contributed to identify characteristic microbiota profiles and shifts in the microbial gene richness in association with cognitive function. Diet, exercise and prebiotics, probiotics or symbiotics significantly influence cognition and changes in the microbiota. Few studies have analyzed the gut microbiota composition in association with cognitive function in humans. Impaired attention, mental flexibility and executive function have been observed in association with a microbiota ecosystem in cross-sectional and longitudinal studies. Nevertheless, the evidence in humans is still scarce and not causal relationships may be inferred, so larger and long-term studies are required to gain insight into the possible role of microbiota in human cognition.

Background: Environmental exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) can disturb the immune response. However, the effect of PAHs on low-grade inflammation related to platelets in humans is unknown., Objectives: We investigated the association of PAH exposure with low-grade inflammation and platelet parameters in healthy preschoolers., Methods: The present study recruited 239 participants, aged 2-7 years, from an electronic-waste (e-waste)-exposed (n = 118) and a reference (n = 121) area. We measured ten urinary PAH metabolites, four types of immune cells and cytokines, and seven platelet parameters, and compared their differences between children from the two groups. Spearman correlation analysis was performed to explore the potential risk factors for PAH exposure and the associations between urinary monohydroxylated PAHs (OH-PAHs) and biological parameters. Associations between urinary PAH metabolites and platelet indices were analyzed using quantile regression models. Mediation analysis was used to understand the relationship between urinary total hydroxynaphthalene (ΣOHNa) and interleukin (IL)-1β through seven platelet indices, as mediator variables., Results: We found higher urinary monohydroxylated PAH (OH-PAH) concentrations, especially 1-hydroxynaphthalene (1-OHNa) and 2-hydroxynaphthalene (2-OHNa), in children from the e-waste-exposed group than in the reference group. These were closely associated with child personal habits and family environment. A decreased lymphocyte ratio and increased pro-inflammatory cytokines, such as gamma interferon-inducible protein (IP)-10 and IL-1β, were found in the e-waste-exposed children. After adjustment for confounding factors, significantly negative correlations were found between levels of mean platelet volume (MPV), platelet distribution width (PDW), platelet-large cell ratio (P-LCR) and ratio of mean platelet volume to platelet count (MPVP) and OH-PAHs. In addition, ΣOHNa was positively associated with IL-1β mediated through MPV, PDW, P-LCR, and ratio of platelet count to lymphocyte count (PLR)., Conclusions: Platelet indices were significantly associated with the changes in urinary OH-PAH levels, which may can be regarded as effective biomarkers of low-grade inflammation resulting from low PAH exposure in healthy children., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Dyslipidaemia and low-grade inflammation are central in atherogenesis and linked to overweight and physical inactivity. Lifestyle changes are important in secondary prevention of coronary artery disease (CAD). We compared the effects of combined weight loss and interval training with interval training alone on physical fitness, body composition, dyslipidaemia and low-grade inflammation in overweight, sedentary participants with CAD., Methods: Seventy CAD patients, BMI 28-40 kg/m 2 and age 45-75 years were randomised to (1) 12 weeks' aerobic interval training (AIT) at 90% of peak heart rate three times/week followed by 40 weeks' AIT twice weekly or (2) a low energy diet (LED) (800-1000 kcal/day) for 8-10 weeks followed by 40 weeks' weight maintenance including AIT twice weekly and a high-protein/low-glycaemic load diet. Effects of the intervention were evaluated by physical fitness, body weight and composition. Dyslipidaemia was described using both biochemical analysis of lipid concentrations and lipoprotein particle subclass distribution determined by density profiling. Low-grade inflammation was determined by C-reactive protein, soluble urokinase-type plasminogen activator receptor and tumour necrosis factor α. Effects on continuous outcomes were tested by mixed-models analysis., Results: Twenty-six (74%) AIT and 29 (83%) LED + AIT participants completed the study. At baseline subject included 43 (78%) men; subjects averages were: age 63 years (6.2), body weight 95.9 kg (12.2) and VO 2 peak 20.7 mL O 2 /kg/min (4.9). Forty-six (84%) had pre-diabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). LED + AIT reduced body weight by 7.2 kg (- 8.4; - 6.1) and waist circumference by 6.6 cm (- 7.7; - 5.5) compared to 1.7 kg (- 0.7; - 2.6) and 3.3 cm (- 5.1; - 1.5) after AIT (within-group p < 0.001, between-group p < 0.001 and p = 0.018, respectively). Treatments caused similar changes in VO 2 peak and lowering of total cholesterol, triglycerides, non-HDL cholesterol and low-grade inflammation. A shift toward larger HDL particles was seen following LED + AIT while AIT elicited no change., Conclusions: Both interventions were feasible. Both groups obtained improvements in VO 2 peak, serum-lipids and inflammation with superior weight loss and greater central fat loss following LED + AIT. Combined LED induced weight loss and exercise can be recommended to CAD patients. Trial registration NCT01724567, November 12, 2012, retrospectively registered (enrolment ended in April 2013).

Background and Aims: Low-grade chronic inflammation is a condition underlying many serious diseases but there is no good single biomarker which can estimate and monitor the severity of the inflammation. C-reactive protein (CRP) is the best validated and most extensively used marker. The aims of the study were to investigate the extent to which CRP levels associate with levels of micronutrients., Methods: We retrieved the levels of S-hsCRP and nutritional variables fB-β-carotenes, fS-Q10 (Ubiquinon), fS-Fe, E-Cu, fS-A vitamin, B-Se, B-Zn, and fB-B12 vitamin from the database of clinical laboratory Mila Oy from the years 1988-2018, a total of nearly 18 800 samples from outpatient clinics, Helsinki and Oulu, Finland. Sample sizes for nutritional variables measured concurrently with S-hsCRP varied between 4356 and 8621. S-hsCRP levels were categorized into five ordered categories. The levels of each micronutrient in those categories were compared using analysis of variance (ANOVA). Males and females were analyzed separately., Results: It was observed that an increase of S-hsCRP associated with the decrease of fS-Fe (p < 0.001 for both genders); fS-A vitamin (p < 0.001 for both genders), and fS-β-carotenes (p < 0.001 for both genders); these are considered negative acute phase reactants. For both genders there was no significant association between the levels of fS-B12 vitamin (p = 0.14 for males; p = 0.03 for females), fS-Q10 (p < 0.001 for males; p = 0.06 for females) and fB-Se (p < 0.001 for males; p = 0.01 for females) and the categorized S-hsCRP. In contrast, fB-Zn (p < 0.001 for both genders) behaved like a positive acute phase reactant whereas copper measured from washed blood cells (E-Cu) did not display any significant associations with S-hsCRP (p = 0.001 for males; p = 0.05 for females)., Conclusions: A linear association was observed for some micronutrients - the higher the degree of low-grade inflammation (S-hsCRP), the more disturbed were the levels of some micronutrients. For clinicians, this finding means that inflammation needs to be acknowledged when assessing micronutrient deficiency. Substitution therapy should be implemented only after the inflammation has been rectified., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Obesity is linked to the development of low-grade, chronic inflammation. Obesity-related inflammation appears to be a different type of inflammation, mainly due to excessive food intake and unusual homeostasis. It can be evaluated by measuring the concentration of pro- and anti-inflammatory marker molecules – C-reactive protein (CRP), serum amyloid-A (SAA) and interleukin-4., Aim: The aim of the present study is to evaluate the rate of the inflammatory process in heart, provoked by the consumption of a high-fat diet., Materials and Methods: Sixty 8-week-old male Wistar rats were used in this experiment. The laboratory animals were fed orally with two different types of rodent food for 14 or 18 weeks – a high-fat diet (experimental groups) and standard rodent food (control groups). They all were kept under standard housing conditions. The levels of the pro- and anti-inflammatory markers in tissue homogenates from heart were analyzed using ELISA. Their expression in tissue samples was detected immunohistochemically by the biotin-streptavidin-peroxidase method. The total protein concentration was determined by the Lawry method., Results: CRP levels showed no significant differences when the control group was compared with the groups fed with a high-fat diet (p>0.05). The SAA levels detected were also insignificantly changed. Only the IL-4 tissue levels showed tendency to increase (p<0.05) in the high-fat diet group., Conclusions: Our experiment indicates that there is a specific reaction of the heart to a high-fat diet. It also refers to the existence of adaptive mechanisms allowing the heart to counteract the development of dietary induced inflammation., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Compelling evidence links elevated levels of C-reactive protein (CRP) and other inflammatory markers to poor treatment outcome of antidepressant medication. Little is known about the contribution of low-grade inflammation to treatment response to electroconvulsive therapy (ECT) in severely depressed patients., Method: Associations between serum levels of CRP, interleukin-6, interleukin-10, and tumour necrosis factor-α as well as remission of depression, time to remission, and speed of decline of depressive symptoms were examined in 95 older (mean age: 73.1 years) depressed patients treated with ECT., Results: Moderately elevated levels of CRP at baseline (3 to 10 mg/L), but no other inflammatory markers, were associated with higher remission rates. In patients with moderately elevated CRP levels, the odds ratio for remission was 3.62 (95% confidence interval [CI], 1.09-11.97; p = 0.04). Time to remission was shorter in those with moderately elevated CRP levels (p = 0.05). Speed of decline was higher in patients with moderately elevated CRP levels as compared with those with low CRP levels (decline of 3.2 Montgomery Åsberg Depression Rating Scale points per administration vs. 2.3 points per administration, p = 0.03)., Limitations: Because of the observational design, residual confounding through other lifestyle or demographic factors cannot be ruled out., Conclusions: Although earlier studies showed that low-grade inflammation contributes to poor treatment response in those treated with antidepressants, our study provides clues that low-grade inflammation does not have such a detrimental effect on the treatment response to ECT. This is underscored by our finding that moderately elevated CRP levels were associated with increased remission rates in depressed patients treated with ECT. Replication studies are warranted., (Copyright © 2019. Published by Elsevier B.V.)

Background and Aims: Evidence regarding the impact of regional body fat distribution on low-grade inflammation is limited. The current study examined the association of central and peripheral body fat distribution and low-grade inflammation levels in young adults, considering collinearity between variables., Methods and Results: A cross-sectional analysis of 809 adults (aged 27 years) was conducted as part of the EPITeen cohort, Porto, Portugal. Regional body fat was measured by dual-energy X-ray absorptiometry scan (DXA) and serum high-sensitivity C-reactive protein (hsCRP) was measured in a fasting blood sample. OLS (ordinary least squares) and LASSO (least absolute shrinkage and selection operator) regression models were fitted to estimate the association of trunk and peripheral fat with hsCRP, stratified by sex. Using OLS regression, trunk fat in females was positively associated with ln(hsCRP) (β 1  = 0.064, 95% CI 0.018; 0.109). The effect of peripheral fat on ln(hsCRP) was shown not to be significantly different from trunk fat (β 2  = -0.011, 95% CI -0.110; 0.089), but no statistically significant association was observed (β 3  = 0.053, 95% CI -0.004; 0.110) between peripheral fat and ln(hsCRP). In males, trunk fat also showed a positive association with ln(hsCRP) (β 1  = 0.104, 95% CI 0.055; 0.154), and the effect of peripheral fat on ln(hsCRP) was shown to be significantly different from trunk fat (β 2  = -0.124, 95% CI -0.237;-0.011). However, the association between peripheral fat and ln(hsCRP) did not reach statistical significance (β 3  = -0.020, 95% CI -0.086; 0.046). The results of OLS were confirmed by LASSO regression., Conclusion: A higher fat deposited in the trunk was positively associated with hsCRP, whereas no statistically significant effect was observed for peripheral fat., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis., Methods: We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L)., Results: After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21-34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22-1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47-69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18-1.82)., Conclusions: About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.

Aim: Our aim is to demonstrate that a healthy diet might reduce the relation between adiposity and inflammation, whereas an unhealthy diet may increase the effect of adiposity on inflammatory biomarkers., Methods: In 618 adolescents (13-17 years) of the European HELENA study, data were available on body composition, a set of inflammation markers, and food intake determined by a self-administered computerized 24-h recall. A 9-point Mediterranean diet score and an antioxidant-rich diet score were used as dietary parameters and tested as moderator. Total body fat was represented by the sum of six skinfold thicknesses and central adiposity by waist circumference. A set of inflammation-related biomarkers was used as outcome: a pro/anti-inflammatory interleukins ratio, TGFβ-1, C-reactive protein, TNF-α, 3 cell adhesion molecules, and 3 types of immune cells; gamma-glutamyltransferase (GGT) and homocysteine were used as cardiovascular disease risk biomarkers, and alanine transaminase (ALT) as liver dysfunction biomarker. Multiple linear regression analyses tested moderation by diet in the adiposity-inflammation association and were adjusted for age, sex, country, puberty, socioeconomic status., Results: Both the Mediterranean and antioxidant-rich diet, and overall and central adiposity, were important in the moderation. Diet was a significant protective moderator in the effect of adiposity on the pro/anti-inflammatory interleukins ratio, TGFβ-1, GGT, and ALT., Conclusion: In conclusion, in some cases, a diet rich in antioxidants and essential nutrients may attenuate the concentration of inflammatory biomarkers caused by adiposity, whereas a poor diet appears to contribute to the onset of early oxidative stress signs.

Aim: To assess if a healthy diet might attenuate the positive sedentary-inflammation relation, whereas an unhealthy diet may increase the effect of sedentary behaviors on inflammatory biomarkers., Methods: In 618 adolescents (13-17 years) of the European HELENA study, data were available on body composition, a set of inflammation markers, and food intake assessed by a self-administered computerized 24 h dietary recall for 2 days. A 9-point Mediterranean diet score and an antioxidant-rich diet z-score were used as dietary indices and tested as moderators. A set of low-grade inflammatory characteristics was used as outcome: several cytokines in an inflammatory ratio (IL-6, IL-10, TNF-α, TGFβ-1), C-reactive protein, three cell-adhesion molecules (sVCAM-1, sICAM-1, sE-selectin), three cardiovascular risk markers (GGT, ALT, homocysteine) and three immune cell types (white blood cells, lymphocytes, CD3). Sedentary behaviors were self-reported and analyzed as total screen time. Multiple linear regression analyses tested moderation by diet in the sedentary behaviors-inflammation association adjusted for age, sex, country, adiposity (sum of six skinfolds), parental education, and socio-economic status., Results: Both diet scores, Mediterranean and antioxidant-rich diet, were significant protective moderators in the effect of sedentary behaviors on alanine-transaminase enzyme (P = 0.014; P = 0.027), and on the pro/anti-inflammatory cytokine ratio (P = 0.001; P = 0.004), but not on other inflammatory parameters., Conclusion: A higher adherence to the Mediterranean diet or an antioxidant-rich diet may attenuate the onset of oxidative stress signs associated by sedentary behaviors, whereas a poor diet seems to increase inflammation.

Background: Saturated fatty acids (SFA) have been reported to promote inflammation. Nevertheless, evidence linking dietary SFA and low-grade inflammation in adolescents is scarce and inconsistent. The modulatory role of physical activity (PA) on fat metabolism and inflammation may provide a potential explanation. Thus, we assessed the association of dietary SFA with high-sensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation, in 15-year-olds, and evaluated possible interactions between dietary SFA and different levels of PA., Methods: Children participating in the 15-year follow-ups of the GINIplus and LISA German birth cohort studies were included (N = 824). SFA intake was estimated by means of a food frequency questionnaire and PA recorded by accelerometers. Average daily minutes of PA were classified into "sedentary", "light" and "moderate-to-vigorous" (MVPA), using Freedson's cut-offs. HsCRP concentrations were measured in serum and categorized into 3 sex-specific levels (below detection limit (I), above 75th percentile (III), in between (II)). Sex-stratified cross-sectional associations between SFA and hsCRP were assessed using multinomial logistic regression, adjusting for potential confounders. Interaction terms were included between SFA and the different PA levels; and if significant interactions were observed, analyses stratified by tertiles of the relevant PA levels were performed. Relative risk ratios (RRR) and 95% confidence intervals (95%CI) were presented for a 1% increase in SFA., Results: An inverse association was observed between SFA intake and hsCRP (II vs. I) in males (RRR = 0.85 [95%CI = 0.76;0.96], p = 0.008), whereas no significant association was observed in females. A significant interaction was observed with "sedentary" and "light" PA but not with MVPA in both sexes (p < 0.05). Stratified analyses indicated a significant inverse association between SFA and medium hsCRP levels in males in the highest light PA tertile (hsCRP II vs. I: 0.67 [0.517;0.858], p = 0.002)., Conclusion: Our findings do not support a detrimental role of dietary SFA in low-grade inflammation among adolescents. In males, higher dietary SFA was associated with lower hsCRP, although this should be interpreted in the context of possibly correlated nutrients. Children spending the most time in light PA drove the observed inverse association, suggesting a synergistic effect of SFA and lifestyle PA in the resultant inflammatory response.