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Summary Purpose To describe the relationship between the severity of lung damage and cytokine levels in sputum, bronchoalveolar lavage fluid (BALF), serum. Method Eight severe patients infected with coronavirus disease 2019 (COVID-19) were admitted and their cytokines and chest computed tomography (CT) were analyzed. Results Compared with in serum, IL-6 and TNF-α in sputum and in BALF show more directly reflect the severity of COVID-19 critical patients. The gradient ratio of IL-6 levels may predict the prognosis of severe patients. Conclusion Cytokine levels in the sputum may be more helpful for indicating lung damage. Local intervention through the respiratory tract is expected to benefit patients with severe COVID-19.

HD patients have impaired adaptive immune responses, which might depend on the primary cause of chronic kidney disease (CKD). We analyzed percentages of T cells subpopulations with the expression of CD69, CD25, CD95, and HLA-DR antigens in HD patients to determine the status of T cell activation. Also, we determined serum levels of cytokines: IL12p70, TNF, IL-10, IL-6, IL-1β, IL-8. HD patients had increased percentages of CD4+CD25+, CD4+CD69+, CD4+HLA-DR+, CD8+CD69+, and CD8+HLA-DR+ cells compared to healthy people. Also, their IL-6 and IL-8 serum levels were higher. Changes in T cell subpopulations were seen in patients with diabetic nephropathy (DN) or ischemic nephropathy (IN) but not with glomerulonephritis (GN). HD patients dialyzed for more than six months had a lower percentage of CD4+CD69+, CD8+HLA-DR+, CD8+CD95+ cells, higher IL-12p70 levels, and lower IL-8 levels. Our results show that HD treatment and CKD cause influence T cell activation status.

Background Inflammatory cytokines have been implicated in organ fibrosis; however, their role in the development of arthrofibrosis after total knee arthroplasty (TKA) has not been well explored. The purpose of this study is to assess whether perioperative synovial fluid or blood plasma cytokine levels are associated with reduced early post-TKA range of motion. Methods A total of 179 patients with end-stage idiopathic osteoarthritis undergoing TKA were enrolled in this prospective cohort study. Synovial fluid and blood plasma were collected prearthrotomy and plasma was collected longitudinally in the postacute care unit and on postoperative days (PODs) 1 and 2. Stiffness was defined as ≤95° range of motion measured with a goniometer at 6 weeks (±2 weeks). Results Thirty-two of 162 (19.8%) patients analyzed were stiff at 6 weeks postoperatively. Postoperative plasma levels of 9 cytokines (Eotaxin3, IL-5, IL12_23p40, IP10, VEGF, IL-7, IL-12p70, IL-16, IL-17a) were significantly different between stiff and nonstiff patients on POD1 and/or POD2. An association between preoperative plasma and synovial fluid cytokine levels and the development of postoperative stiffness was not detected. Conclusion The results of this study suggest that there is a distinct acute postoperative cytokine response profile in patients who develop stiffness 6 weeks after TKA. This profile was characterized by significant differences in levels of 9 cytokines over the first 2 postoperative days. These results identify cytokines that are potential biomarkers for risk of early stiffness after TKA and may play a role in the pathophysiology of this outcome.

To analyse the tear cytokine levels of patients diagnosed with ocular chronic graft-versus-host disease(GVHD)and examine the consistency of these levels with different ocular surface parameters.23 ocular chronic GVHD patients were selected for the assessment of tear cytokine levels and ocular surface parameters (TBUT, CFS, OSDI, and Schirmer's test), and 16 dry eye disease(DED)patients without systemic immune disease were selected as the control group. The 23 cytokines were measured using microsphere-based immunoassay analysis and their consistency with different ocular surface parameters was studied.ICAM-1, IL-1β, IL-6, and IL-8 showed elevated levels in the eyes of oGVHD patients compared to DED [P 0.001]. IL-7 and EGF showed lower levels in the eyes of patients with oGVHD than in those of patients with DED [P 0.0001]. Furthermore, the levels of IL-6 and IL-8 showed a stronger correlation with corneal fluorescein staining (CFS) (P 0.05), and the levels of IL-6 and ICAM-1 were most consistent with fluorescein tear film break-up time (TBUT) (P 0.05).Our study demonstrated certain tear cytokines, including ICAM-1, IL-1β, IL-6, IL-8 IL-7 and EGF, as promising new possible diagnostic markers of chronic oGVHD and criteria for chronic ocular GVHD severity. Because tear sampling is noninvasive and simple, this method is expected to be an overwhelming applicable for the screening and diagnosis of chronic GVHD.

Increasing evidence suggests that immunological disturbances and abnormalities in axonal myelination are involved in the pathophysiology of autism spectrum disorder (ASD). The present study aimed to determine the role of cytokines in myelin damage in Chinese children with ASD and the role of cytokine dysregulation, myelin damage, and cytokine polymorphisms in ASD in Chinese children. The present case-control study included 98 ASD subjects and 252 typically developing (TD) controls; the levels of serum cytokines and myelin basic protein (MBP) were determined using enzyme-linked immunosorbent assay. Cytokine polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Autistic clinical manifestations were assessed by the Childhood Autism Rating Scale (CARS). The results showed that serum levels of interleukin (IL)-1β, IL-2R, IL-6, IL-8, and MBP were higher in children with ASD compared with those in TD children. In individuals with ASD, serum MBP level was significantly positively associated with the CARS total score, and serum levels of IL-1β, IL-2R, IL-6, and MBP demonstrated positive correlations. The data identified IL-6*MBP as a factor that influenced the risk of ASD, and IL-2R*MBP was identified as a factor that influenced symptom severity, which influenced auxiliary diagnosis of ASD. The presence of the interleukin-6-572CC genotype was associated with significantly higher serum levels of IL-6 and MBP but did not influence the risk and symptom severity of ASD. Therefore, the results suggested inflammatory responses and myelin damage in Chinese children with ASD. Cytokine dysregulation influenced myelin damage in ASD; moreover, the interactions of the cytokines and myelin damage influenced the risk and symptom severity of ASD. The IL-6-572C/G genotypes may be associated with myelin damage in ASD by influencing the circulating level of IL-6.

Introduction The role of immunological mechanisms in the pathophysiology of mental disorders has been discussed with increasing frequency. In this context, especially schizophrenia has become the focus of attention after the discovery of autoimmune encephalitis, which might present with psychotic symptoms. Furthermore, multiple studies have identified associations between infections or autoimmune diseases and schizophreniform disorders. Cerebrospinal fluid (CSF) analysis plays a central role in identifying potential inflammatory processes in the central nervous system. Therefore, the rationale of this retrospective study was the analysis of different cytokines, including interleukin-8 (IL-8) levels, in the CSF of patients with schizophrenia spectrum disorders. Methods The authors examined the CSF of 40 patients with schizophrenia spectrum disorders, in comparison to the CSF of a mentally healthy control group of 39 patients with idiopathic intracranial hypertension (IIH). Magnetic bead multiplexing immunoassay was used to retrospectively determine different cytokines in the participants' CSF. Results Participants with schizophrenia spectrum disorders had significantly higher IL-8 levels in their CSF than controls (mean ± SD: 41.83 ± 17.50 pg/ml versus 21.40 ± 7.96 pg/ml; p Conclusion The main finding of this study is the presence of significantly higher IL-8 concentrations in the CSF of patients with schizophrenia spectrum disorders when compared to the control group. This supports the hypothesis that immunological processes may be involved in the pathophysiology of a subgroup of patients with schizophrenia spectrum disorders. However, the study's results are limited by the retrospective design, methodological aspects, and the control group with IIH.

Background Evidence suggests that depression is correlated with immune-inflammatory responses, and efforts have been made to identify the relationships between depression and inflammatory markers. This study investigated the level of cytokines before and after treatment for major depressive disorder (MDD) in medication-naive adolescents with first-episode MDD and compared them with the levels in healthy adolescents. The relationship between cytokine levels and the severity of depressive symptoms was also examined. Methods Twenty-five adolescents with MDD and 25 healthy controls aged 13 to 18 years were included in the study. Blood samples were obtained, and depression severity was assessed twice in the MDD group before and after treatment and once in the healthy group. Results When compared with healthy controls, adolescents with MDD had lower levels of interleukin 2 (IL-2), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and IL-10 before treatment and higher levels of IL-2, IFN-γ, and IL-10 after treatment. In addition, the IFN-γ levels correlated with depressive severity scores in both the Children's Depression Inventory (CDI) and Hamilton Depression Rating Scale (HDRS). The IL-10 level correlated with depressive severity only on the HDRS. Limitations The sample size was small, and the 12-week follow-up time after treatment was relatively short. Conclusion IL-2, IFN-γ, TNF-α, and IL-10 levels in medication-naive adolescents with first-episode MDD differed from those in healthy controls. The levels of IL-2, IFN-γ, and IL-10 were altered after antidepressant treatment. Further, the IFN-γ and IL-10 levels correlated with the severity of depressive symptoms.

To compare cytokine levels in the pre-corneal tear film between patients with allergic rhinitis, allergic rhinoconjunctivitis and the normal population.A comparative cross sectional study.Patients were divided into Group 1 (allergic rhinitis without conjunctivitis), Group 2 (allergic rhinoconjunctivitis), and Group 3 (normal population).A comparative cross-sectional study was conducted. Patients were divided into; Group 1 (allergic rhinitis without conjunctivitis), Group 2 (allergic rhinoconjunctivitis), and Group 3 (normal controls). Tears were collected using Schirmer strips and cytokine analysis performed using enzyme linked immunosorbent assay.There were a total of 68 subjects. Median values of cytokines in the allergic rhinitis group were as follows; TNFa (45.34 pg/ml), IL-4 (61.91 pg/ml), IL-5 (8.92 pg/ml), IL-6 (538.37 pg/ml) and IL-8 (1438.72 pg/ml). Cytokine levels in the group with allergic rhinoconjunctivitis were approximately two-fold higher than in the group with allergic rhinitis only. The median cytokine level in the control group was lowest. A significant inter-group difference was observed for TNF-alpha, IL-4, IL-6 and IL-8 levels, with allergic rhinoconjunctivitis patients demonstrating significantly elevated cytokines compared to those with allergic rhinitis only (p0.001). These four cytokines were also significantly higher in those with allergic rhinitis than in controls (p0.005). Although the group with allergic rhinoconjunctivitis had the highest levels of IL-5, no statistically significant inter-group difference was noted (p=0.479).This study demonstrated the presence of raised tear film inflammatory cytokines even in allergic rhinitis patients without ocular symptoms. These patients may be at increased risk of developing allergic conjunctivitis. These findings not only substantiate the immunological theory of the naso-ocular reflex, but have clinical and therapeutic implications for the holistic management of allergic rhinitis and conjunctivitis.

An exceptionally high mortality rate is observed in sepsis and septic shock. Systemic administration of lipopolysaccharide (LPS) has been used as an experimental model for sepsis resulting in an exacerbated immune response, brain neurochemistry adjustments, hypotension, and hypothermia followed by fever. Central serotonergic pathways not only modulate systemic inflammation (SI) but also are affected by SI, including in the anteroventral region of the hypothalamus (AVPO), which is the hierarchically most important region for body temperature (Tb) control. In this study, we sought to determine if central serotonin (5-HT) plays a role in SI induced by intravenous administration of LPS (1.5 mg/kg) in male Wistar rats (280–350 g) by assessing 5-HT levels in the AVPO, mean arterial pressure, heart rate, and Tb up to 300 min after LPS administration, as well as assessing plasma and spleen cytokine levels, nitric oxide (NO) plasma levels, and prostaglandin (PG) E2 levels in the AVPO at 75 min and 300 min after LPS administration. We observed reduced AVPO 5-HT levels, hypotension, tachycardia, hypothermia followed by fever, as well as observing increased plasma NO, plasma and spleen cytokines and AVPO PGE2 levels in SI. Intracerebroventricular (icv) administration of 5-HT 30 min before LPS administration prevented hypotension and hypothermia, which were accompanied by reduced plasma NO, as well as plasma TNF-α, IL-1β, IL-6, and IL-10 and spleen TNF-α and IL-10 levels. We suggest that SI reduced 5-HT levels in the AVPO favor an increased pro-inflammatory status both centrally and peripherally that converge to hypotension and hypothermia. Moreover, our results are consistent with the notion that exogenous 5-HT given icv prevents hypotension and hypothermia probably activating the splenic anti-inflammatory pathway.

COVID-19 is the respiratory illness caused by the novel coronavirus, SARS-CoV-2. Cytokine storm appears to be a factor in COVID-19 mortality. Echinacea species have been used historically for immune modulation. A previous rapid review suggested that Echinacea supplementation may decrease the levels of pro-inflammatory cytokines involved in cytokine storm. The objective of the present systematic review was to identify all research that has assessed changes in levels of cytokines relevant to cytokine storm in response to administration of Echinacea supplementation. The following databases were searched: Medline (Ovid), AMED (Ovid), CINAHL (EBSCO), EMBASE (Ovid). Title and abstract screening, full text screening, and data extraction were completed in duplicate using a piloted extraction template. Risk of bias assessment was completed. Qualitative analysis was used to assess for trends in cytokine level changes. The search identified 279 unique publications. After full text screening, 105 studies met criteria for inclusion including 13 human studies, 24 animal studies, and 71 in vitro or ex vivo studies. The data suggest that Echinacea supplementation may be associated with a decrease in the pro-inflammatory cytokines IL-6, IL-8, and TNF, as well as an increase in the anti-inflammatory cytokine IL-10. The risk of bias in the included studies was generally high. While there is currently no substantive research on the therapeutic effects of Echinacea in the management of either cytokine storm or COVID-19, the present evidence related to the herb's impact on cytokine levels suggests that further research may be warranted in the form of a clinical trial involving patients with COVID-19.

Longitudinal associations of cytokine levels with depression are unclear. This study aimed to investigate cross-sectional and prospective associations between five serum pro-inflammatory cytokine levels and late-life depression. 732 Korean people aged 65+ were evaluated at baseline. Of 631 without depression (Geriatric Mental State schedule) at baseline, 521 (83%) were followed over a 2 year period and incident depression was ascertained. Serum tumor necrosis factor-α, interleukin (IL)-1α, IL-1β, IL-6, and IL-8 levels were assayed at both baseline and follow-up. Associations between cytokine levels and depressive status were evaluated using linear regression models, considering potential covariates (demographics, cognitive function, disability, lifestyle factors, and vascular risk factors) and applying Bonferroni corrections. Prevalent depression at baseline was significantly associated with higher contemporaneous levels of IL-1β and IL-8, independent of relevant covariates and after applying Bonferroni corrections. In the analyses of the five cytokine levels in combination, independent associations were found between prevalent depression and increased numbers of cytokines at higher levels at baseline. Incident depression was significantly associated with increases in IL-1β, IL-6, and IL-8 levels during the follow-up independent of relevant covariates and after applying Bonferroni corrections. In combination analyses, incident depression was independently associated with higher numbers of cytokines showing increasing levels over the same follow-up period. However, incident depression was not predicted by higher baseline pro-inflammatory cytokine levels in any analysis. Our findings suggest that depression might affect serum cytokines alterations and lead to inflammatory processes in late-life.

Background Inflammation has been hypothesized to contribute to reward dysfunction across psychiatric conditions, but little is known about this relationship in youth. Therefore, the present study investigated the associations between general and specific markers of inflammation and neural activation during reward processing, including anticipation and attainment, in youth with diverse psychiatric symptoms. Methods Forty-six psychotropic medication-free youth with diverse psychiatric symptoms underwent a blood draw to measure 41 cytokines, as well as structural and functional magnetic resonance imaging. The Reward Flanker Task examined neural activation during reward anticipation and attainment. Relationships between inflammation and neural activation were assessed using data reduction techniques across the whole-brain, as well as in specific reward regions of interest (basal ganglia, anterior and mid-cingulate cortex [ACC/MCC]). Results Whole-brain principal component analyses showed that factor 3 (12 cytokines: FGF-2, Flt3-L, fractalkine, GM-CSF, IFN-α2, IFN-γ, IL-3, IL-4, IL-7, IL-17A, MDC, and VEGF) was negatively correlated with precuneus/posterior cingulate cortex activity during anticipation. Factor 2 (11 cytokines: eotaxin, IL-1α, IL-1Rα, IL-2, IL-5, IL-9, IL-12p40, IL-13, IL-15, MCP-3, and TNF-β) was negatively correlated with angular gyrus activity during attainment. ROI analyses additionally showed that multiple cytokines were related to activity in the basal ganglia (EGF, FGF-2, Flt-3L, IL-2, IL-13, IL-15, IL-1Rα, MCP-3) and ACC/MCC (Flt-3L) during attainment. C-reactive protein (CRP) was not associated with neural activation. Conclusions Investigation of specific markers of immune function showed associations between inflammatory processes and activation of posterior default mode network, prefrontal cortex, and basal ganglia regions during multiple phases of reward processing.

Purpose We sought to investigate the association between the severity of bullous keratopathy and proinflammatory cytokine levels in the aqueous humor (AqH). Design Cross-sectional study. Methods This study included a total of 95 eyes: 62 with bullous keratopathy and 33 that underwent cataract surgery. Central corneal thickness (CCT) and central corneal volume within 4 and 6 mm (CCV4mm and CCV6mm, respectively) were determined using anterior segment optical coherence tomography. A total of 95 AqH samples were collected at the beginning of surgery. The levels of cytokines (interleukins [ILs]-1α, -1β, -4, -6, -8, -10, -12p70, -13, -17A, interferon [IFN]-α, IFN-γ, monocyte chemotactic protein [MCP]-1, E-selectin, P-selectin, and soluble intercellular adhesion molecule-1 [sICAM-1]) in the AqH were measured using multiplex beads immunoassay. We evaluated the correlation among AqH cytokine levels, CCT, CCV4mm, and CCV6mm in eyes with bullous keratopathy. Results The levels of protein, ILs-4, -6, -8, -10, -12p70, and -17A, MCP-1, IFN-γ, E-selectin, P-selectin, and sICAM-1 were significantly higher in eyes with bullous keratopathy compared with those of the normal control subjects (all P Conclusion The severity of corneal edema in eyes with bullous keratopathy was associated with the levels of specific cytokines in the AqH.

Object Goal of this research was to investigate values of serum cytokines in childhood HLH with different triggers, with the expectation to find secretion spectrum of 5 main types of underlying diseases. Method 118 newly diagnosed HLH were included, and serum concentrations of 6 cytokines were tested before treatment began. Absolute cytokine levels and ratios between them were then studied in the HLH groups collectively and separately Results In general, IFN-γ, IL-10 and IL-6 showed differences among 5 HLH groups. Specifically, relative levels of these three cytokines to each other were meaningful in distinguishing 4 types of HLH. Level of IL-6 was higher than those of IFN-γ or IL-10 in HLH driven by Systemic auto-inflammatory disorders (SAIDs) or Langerhans Cell Histiocytosis (LCH), while primary HLH and EBV-HLH shared elevated ratio of IL-10 to IL-6. Although more than one distinctive ratios were found in 3 HLH groups, combination of these parameters didn’t offer optimal balance between sensitivity and specificity. Conclusion As a group of easily gained laboratory findings, cytokine levels were reliable in the procedure of roughly classifying HLH cases with the help of patients’ clinical phenotype. However, adequate data is still needed to explore the significance of these indicators in identifying one particular underlying disease accurately.

Made available in DSpace on 2022-04-29T08:36:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Objective: Patterns of cytokine levels and their association with stroke severity, infarct size, and muscle strength are obscure. We aimed to analyze the immune mediators linked to T helper (Th)1, Th2, Th17, and regulatory T cell patterns and their association with stroke severity, infarct size, and muscle strength. Materials and methods: We included patients with acute stroke (n = 15) and healthy non-disabled individuals (n = 20) aged > 18 years. The dependent variables were stroke severity according to the National Institute of Health Stroke Scale (NIHSS), infarct size on computed tomography, handgrip strength by dynamometry, and global muscle strength according to the Medical Research Council (MRC) scale. The independent variables were the circulating cytokine levels. The cytokine levels were compared between the groups, and correlations between the clinical data were verified. Results: The stroke group had higher interleukin (IL)-6 (p < 0.0001) and IL-10 (p < 0.0001) levels, but lower tumor necrosis factor (TNF)-α (p = 0.036) levels than the control group. IL-10 and soluble tumor necrosis factor receptor (sTNF-RII) levels were correlated with each other (r = 0.533; p = 0.042) and infarct size (r = 0.653; p = 0.033 and r = 0.689; p = 0.018, respectively). MRC scores were positively and negatively correlated with handgrip strength of the affected side (r = 0.78; p = 0.001) and NIHSS scores (r = -0.87; p < 0.0001), respectively. Conclusions: Plasma levels of some cytokines were associated with changes in the acute phase of stroke, and IL-10 and sTNF-RII levels are potential biomarkers of infarct size. Department of Applied Physical Therapy Federal University of Triângulo Mineiro Department of Microbiology Immunology and Parasitology Federal University of Triângulo Mineiro Department of Neurology Psychology and Psychiatry Botucatu Medical School Clinics Hospital of the Federal University of Triângulo Mineiro Department of Neurology Psychology and Psychiatry Botucatu Medical School

Introduction In recent years researchers have focused at hormonal activity in Cushing’s syndrome (CS) in connection with metabolic disorders and the role of adipokines and cytokines secreted by the adipose tissue. The aim of the study was to investigate levels of adipokines and cytokines in patients with: subclinical CS (SCS) – in relation to hormonal parameters of hypercortisolemia, and, adrenocortical cancer (ACC). Materials and methods The study included 20 SCS as well as 7 ACC patients, and 18 healthy participants. Hormonal activity and serum concentrations of adiponectin, leptin, resistin, tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), and monocyte chemoattractant protein 1 (MCP1), were analyzed. Results In SCS patients compared to healthy volunteers a trend toward higher concentrations of all pro-inflammatory cytokines was noted, however, statistically significant differences were only found for TNFα and IL6 (p = 0.047 and p = 0.028, respectively). Adiponectin concentrations were significantly lower in the SCS group (p = 0.006). Serum adipokine and cytokine levels were independent of the presence of diabetes mellitus (DM) and hypertension (HT) in the SCS group. A significant correlation was found between subclinical glucocorticoid secretion and IL6 concentration (Pearson’s r = 0.517, p = 0.02). Acquired results were independent of BMI. In ACC patients compared to controls higher IL6, TNFα and MCP1 levels were recorded. Conclusion It is possible that higher adipokine and pro-inflammatory cytokine concentrations as well as lower anti-inflammatory adiponectin concentrations comprise an additional risk factor of metabolic and cardiovascular diseases in SCS patients. It seems that at least among patients with SCS adipokine and cytokine secretion is independent of hormonal activity (except for IL6).

The pathophysiology of neuropsychiatric disorders is unclear. Increasing evidence has suggested maternal immune system dysregulation may be implicated in offspring's early brain development and related to an increased risk of neuropsychiatric disorders in offspring. The primary objective of this meta-analysis was to investigate the association of maternal CRP and cytokine levels with offspring's neuropsychiatric disorders. We identified relevant studies following a search of PubMed, Web of Science, EMbase database between January 1971 and February 2018. A meta-analysis was performed on studies which reported the association of prenatal maternal peripheral blood concentrations of CRP and cytokines with offspring's neuropsychiatric disorders. Results were reported according to PRISMA statement. Fifteen studies (six for maternal CRP, nine for maternal cytokines) were included in the meta-analysis, of which 80% were of high methodological quality. Random-effect meta-analysis showed that increasing maternal CRP (OR = 1.31, 95% CI 1.11-1.55, SMD = 0.15, 95% CI 0.06-0.24, P 0.01), pro-inflammatory cytokine interleukin (IL)-8 (OR = 1.64, 95% CI 1.06-2.55, SMD = 0.27, 95% CI 0.03-0.52, P = 0.03) and anti-inflammatory cytokine IL-10 (OR = 2.16, 95% CI 1.30-3.59, SMD = 0.43, 95% CI 0.14-0.71, P 0.01) were significantly associated with schizophrenia in offspring. The finding of our meta-analysis has identified significantly altered maternal CRP and cytokine concentrations in schizophrenia, strengthening evidence of maternal immune system dysregulation in neuropsychiatric disorders where inflammatory signals dominate.

Background: ABO blood groups are associated with different risk of viral infections. In vitro studies demonstrated how anti-A and anti-B antibodies neutralized the infectious capacity of SARS-CoV-2. Therefore, here we describe the inflammatory response of COVID-19 patients in the context of the blood group aiming to assess the lower severity status found in group O patients. Methods: Prospective and consecutive study including blood samples from 108 adult patients diagnosed with COVID-19 and admitted to the “Hospital Clinico Universitario” Valladolid, Spain between March 24 and April 11 2020. Patients were divided according to their ABO blood group. Plasma aliquots were analyzed, in duplicate, for the quantification of 45 mediators by MAGPIX system (Luminex). Statistical analysis was performed using the R statistical package version 4.0.2 Findings: We found a lower risk (2.16 times) of mechanical ventilation or death in patients with blood group O [Log Rank: p=0.042, Hazard Ratio: 0.463, CI 95% (0.213-1.004), p=0.050]. Moreover, 15 cytokines were significantly over-expressed (and only one under-expressed) in blood group O. Last, a multivariate model found BDNF, IL-13 and IL-27 as the best cytokines able to differentiate the immune profile based on blood group. Interpretation: Our cohort showed how blood group O was associated with both lower rates of hospital admission and a lower risk of intubation or death. Indeed, these patients produced higher amounts of cytokines in response to SARS-CoV-2, hence mounting an effective immune response which allowed them to control the viral infection and therefore decrease the risk of further complications. Funding Statement: This research was funded by Instituto de Salud Carlos III, grant number COV20/00491. Declaration of Interests: Alvaro Tamayo-Velasco declares no conflict of interest. - Maria Jesus Penarrubia-Ponce declares no conflict of interest. - Francisco Javier Alvarez declares no conflict of interest. - Hugo Gonzalo-Benito declares no conflict of interest. - Ignacio de la Fuente declares no conflict of interest. - Sonia Perez Gonzalez declares no conflict of interest. - Lucia Rico declares no conflict of interest. - Maria Teresa Jimenez-Garcia declares no conflict of interest. - Alba Sanchez-Rodriguez declares no conflict of interest. - Milagros Hijas-Villaizan declares no conflict of interest. - Marta Martin Fernandez declares no conflict of interest. - Carlos Duenas declares no conflict of interest. - Esther Gomez-Sanchez declares no conflict of interest. - Maria Heredia-Rodriguez declares no conflict of interest. - Oscar Gorgojo-Galindo declares no conflict of interest. - Itziar Fernandez declares no conflict of interest. - Lourdes del Rio declares no conflict of interest. - Irene Carnicero-Frutos declares no conflict of interest. - Maria Fe Munoz-Moreno declares no conflict of interest. - Eduardo Tamayo declares no conflict of interest. - David Bernardo declares no conflict of interest. - Pedro Martinez-Paz declares no conflict of interest. Ethics Approval Statement: The study was approved by the Hospital's Clinical Ethics Committee (CEIm) and approval was obtained from all study participants (cod: PI 20-1717).

Background Prenatal life stress exposure is linked to dysregulated immune function and chronic inflammatory disease in offspring, but we know little about its effects on infant immune response during viral infection. Method To address this issue, we examined associations between prenatal life stress exposure and infant upper-airway inflammatory markers during acute respiratory infection (ARI) using data from a prospective, population-based birth-cohort study (N = 180). Infant inflammation was measured as a continuous latent factor within a structural equation modeling framework using nasal wash concentrations of interleukin-1β, interleukin-6, and tumor necrosis factor-α. We hypothesized that infants exposed to prenatal life stress would have greater levels of nasal inflammation during ARI and increased risk for ARI-related morbidity in early childhood. Results Our findings contradicted these hypotheses and provided evidence of sexually dimorphic effects of prenatal stress exposure on infant immune functioning during ARI. Among boys, but not girls, prenatal stress was negatively associated with nasal inflammation and indirectly associated with both lower ARI severity and reduced likelihood of subsequent ARI-related hospitalization in the 2nd and 3rd years of life. Conclusion These data suggest that prenatal stress exposure may be beneficial for infant boys in the context of respiratory viral infections; however, it will be critical to determine if these benefits are offset by increased risk for chronic inflammatory diseases in later childhood. As the participants in this cohort are being followed longitudinally through age 8, we will be able to evaluate long-term health outcomes in future studies.

The aim of this study was to evaluate the effect of carvacrol on serum levels of interleukins (IL-2, IL-4, IL-6, IL-8, and IL-10), interferon-gamma (IFNγ) levels and pulmonary function tests (PFT) in patients who were exposed to sulfur mustard (SM).Twenty patients exposed to SM 27-30 years ago were divided to placebo and carvacrol (1.2 mg/kg/day) treated groups (n = 10 for each group). Drugs were given in a double-blind manner for two months. Serum levels of cytokines and PFT values including; maximum mid-expiratory flow (MMEF) and maximum expiratory flow at 25, 50 and 75% of vital capacity (MEF25, 50 and 75) were measured at the beginning (step 0), one and two month (steps I and II, respectively) after starting the treatment.The serum levels of IL-2, IL-4, IL-6 and IL-8 were significantly decreased in step I and II compared to step 0 (p 0.05 to p 0.001), while the serum levels of IL-10 and IFNγ were increased in step II compared to step 0 (p 0.01, for both cases) and IFN-γ/IL-4 ratio was enhanced in step II compared to step 0 (p 0.001) in carvacrol treated group. MMEF, MEF75, and 50 values were significant increase in step I and II compared to step 0 (p 0.05 to p 0.001) in carvacrol treated group.Treatment with carvacrol for two months reduced inflammatory cytokine, while increased anti-inflammatory cytokines and improved PFT tests in SM induced lung injury.

Radiation esophagitis (RE) is a common adverse event associated with radiotherapy for non–small cell lung cancer (NSCLC). While plasma cytokine levels have been correlated with other forms of radiation-induced toxicity, their association with RE has been less well studied. We analyzed data from 126 patients treated on 4 prospective clinical trials. Logistic regression models based on combinations of dosimetric factors [maximum dose to 2 cubic cm (D2cc) and generalized equivalent uniform dose (gEUD)], clinical variables, and pretreatment plasma levels of 30 cytokines were developed. Cross-validated estimates of area under the receiver operating characteristic curve (AUC) and log likelihood were used to assess prediction accuracy. Dose-only models predicted grade 3 RE with AUC values of 0.750 (D2cc) and 0.727 (gEUD). Combining clinical factors with D2cc increased the AUC to 0.779. Incorporating pretreatment cytokine measurements, modeled as direct associations with RE and as potential interactions with the dose-esophagitis association, produced AUC values of 0.758 and 0.773, respectively. D2cc and gEUD correlated with grade 3 RE with odds ratios (ORs) of 1.094/Gy and 1.096/Gy, respectively. Female gender was associated with a higher risk of RE, with ORs of 1.09 and 1.112 in the D2cc and gEUD models, respectively. Older age was associated with decreased risk of RE, with ORs of 0.992/year and 0.991/year in the D2cc and gEUD models, respectively. Combining clinical with dosimetric factors but not pretreatment cytokine levels yielded improved prediction of grade 3 RE compared to prediction by dose alone. Such multifactorial modeling may prove useful in directing radiation treatment planning.

Background Evidence supports raised circulating levels of inflammatory mediators, such as interleukin-6 (IL-6) and tumor necrosis factor (TNFα), among clinically depressed adults, although preliminary findings in adolescents are mixed. Independently, meta-analyses identify correlations between childhood trauma and elevated cytokine levels in adulthood. Here, we examine the possible role of individual differences in exposure to childhood trauma in contributing to variability in cytokine levels in depressed adolescents. Methods 52 depressed adolescents and 20 healthy adolescents completed measures of childhood trauma and provided blood for the assessment of plasma IL-6 and TNFα. Cross-sectional associations of childhood trauma and cytokine measures were assessed in both depressed and healthy adolescents, along with exploratory analysis of childhood trauma subtypes. Longitudinal relationships between childhood trauma and cytokine measures were also studied in an exploratory fashion within a subset of depressed participants (n = 36). Results Higher childhood trauma (particularly emotional abuse) was positively associated with TNFα in depressed adolescents. Childhood trauma was not linked to longitudinal changes in cytokine levels. Discussion In depressed adolescents, childhood trauma may relate to higher levels of the proinflammatory cytokine TNFα and contribute to heterogeneity in cytokine elevation among depressed adolescents. Such findings may ultimately help guide more effective individualized treatments for adolescents with depression.

Catecholamines and prostaglandins are secreted abundantly during the perioperative period in response to stress and surgery, and were shown by translational studies to promote tumor metastasis. Here, in a phase-II biomarker clinical trial in breast cancer patients (n = 38), we tested the combined perioperative use of the β-blocker, propranolol, and the COX2-inhibitor, etodolac, scheduled for 11 consecutive perioperative days, starting 5 days before surgery. Blood samples were taken before treatment (T1), on the mornings before and after surgery (T2&T3), and after treatment cessation (T4). Drugs were well tolerated. Results based on a-priori hypotheses indicated that already before surgery (T2), serum levels of pro-inflammatory IL-6, CRP, and IFNγ, and anti-inflammatory, cortisol and IL-10, increased. At T2 and/or T3, drug treatment reduced serum levels of the above pro-inflammatory cytokines and of TRAIL, as well as activity of multiple inflammation-related transcription factors (including NFκB, STAT3, ISRE), but not serum levels of cortisol, IL-10, IL-18, IL-8, VEGF and TNFα. In the excised tumor, treatment reduced the expression of the proliferation marker Ki-67, and positively affected its transcription factors SP1 and AhR. Exploratory analyses of transcriptome modulation in PBMCs revealed treatment-induced improvement at T2/T3 in several transcription factors that in primary tumors indicate poor prognosis (CUX1, THRa, EVI1, RORa, PBX1, and T3R), angiogenesis (YY1), EMT (GATA1 and deltaEF1/ZEB1), proliferation (GATA2), and glucocorticoids response (GRE), while increasing the activity of the oncogenes c-MYB and N-MYC. Overall, the drug treatment may benefit breast cancer patients through reducing systemic inflammation and pro-metastatic/pro-growth biomarkers in the excised tumor and PBMCs.

Preclinical studies demonstrate that environmentally-induced alterations in inflammatory cytokines generated by the maternal and fetal immune system can significantly impact fetal brain development. Yet, the relationship between maternal cytokines during gestation and later cognitive ability and executive function remains understudied. Children (n = 246) were born of mothers enrolled in the Newborn Epigenetic Study – a prospective pre-birth cohort in the Southeastern US. We characterized seven cytokines [ IL - 1 β , IL - 4 , IL - 6 , IL - 12 p 70 , IL - 17 A , tumor necrosis factor-α ( TNF α ) , and interferon-γ ( IFN γ ) ] and one chemokine ( IL - 8 ) from maternal plasma collected during pregnancy. We assessed children’s cognitive abilities and executive functioning at a mean age of 4.5 (SD = 1.1) years. Children’s DAS-II and NIH toolbox scores were regressed on cytokines and the chemokine, controlling for maternal age, race, education, body mass index, IQ, parity, smoking status, delivery type, gestational weeks, and child birth weight and sex. Higher IL-12p70 ( β IL - 12 p 70 = 4.26, p = 0.023) and IL-17A ( β IL - 17 A = 3.70, p = 0.042) levels were related to higher DAS-II GCA score, whereas higher IL-1 β ( β IL - 1 B = −6.07, p = 0.003) was related to lower GCA score. Higher IL-12p70 was related to higher performance on NIH toolbox measures of executive functions related to inhibitory control and attention ( β IL - 12 p 70 = 5.20, p = 0.046) and cognitive flexibility ( β IL - 12 p 70 = 5.10, p = 0.047). Results suggest that dysregulation in gestational immune activity are associated with child cognitive ability and executive functioning.

Tail biting is detrimental to animal welfare and has negative consequences for producer economy. Poor health is one of the risk factors for tail biting. The first aim of this study was therefore to test for links between health status and behavior related to tail biting at the individual level. The second aim of this study was to test whether variation in cytokines was related to variation in social behavior. These small molecules produced upon immune activation are known to influence behavior both in the direction of withdrawal and increased aggression. This could potentially increase non-functional social behavior and thereby the risk of a tail biting outbreak. To investigate this, we collected behavioral data, health data, feeding data and blood samples from undocked boars at a test station farm in Norway. We compared groups with three different diagnoses: osteochondrosis diagnosed by computer tomography scanning (OCSAN), osteochondrosis diagnosed by clinical examination (OCCLIN) and respiratory tract disease (RESP), with healthy controls (CTR). We tested whether the diagnoses were associated with feeding and growth, social behavior and cytokine levels. We then tested whether there were correlations between cytokine levels and social behavior. We also provide raw data on cytokine levels in the extended sample (N = 305) as there are few publications on cytokine levels measured in pigs living under commercial conditions. OCCLIN pigs visited the feeder less, and fed longer compared to CTR pigs. Pigs diagnosed with RESP showed a large drop in growth the first week after filming, which corresponds to the week they were likely to have been diagnosed with illness, and a tendency to compensatory increase in the week after that. Social behavior differed between experimental groups with OCSCAN pigs receiving more social behavior (both aggressive and non aggressive) compared to CTR, and RESP pigs tending to perform more ear- and tail-biting than controls. There were no differences in absolute levels of cytokines between categories. However IL1-ra and IL-12 showed correlations with several behaviors that have been shown by others to be associated with current or future tail biting activity. To our knowledge, this is the first published study indicating a role for illness in non-functional social behavior in pigs and the first showing a correlation between cytokine levels and social behavior.

Aims Gulf War illness (GWI) is a disorder affecting military personnel deployed in the Gulf War (GW) from 1990 to 1991. Here, we will use a rat model of GWI to evaluate hippocampal function and cytokine levels. Materials and methods Rats were exposed to diethyltoluamide and permethrin via dermal absorption and pyridostigmine bromide via gavage with or without a 5-min restraint for 28 days. Immediate and delayed effects of GW chemical exposure were evaluated using electrophysiology to quantitate hippocampal function, behavioral tests to assess cognitive effects and biochemical assays to measure neurotransmitter and cytokine levels. Key findings Behavioral data revealed a statistically significant increase in motor activity at 3 months following completion of exposures, potentially indicating increased excitability, and/or restlessness. Electrophysiology data revealed statistically significant changes in paired pulse facilitation and input-output function of CA1 hippocampal neurons within 24 h and 3 months following completion of exposures. There was also a statistically significant reduction in the frequency of spontaneous firing activity of hippocampal neurons within 24 h following exposures. Naive hippocampal slices directly incubated in GW chemicals also resulted in similar changes in electrophysiological parameters. Biochemical measurements revealed reduced hippocampal glutamate level at 3 months post-exposure. Furthermore, there was a statistically significant increase in plasma and hippocampal levels of IL-13, as well as decrease in plasma level of IL-1β. Significance Our data support an effect on glutamate signaling within the hippocampus as indicated by changes in PPF and hippocampal level of glutamate, with some activation of T helper type 2 immune response.

Objective: To assess the effects of dexmedetomidine (Dex) on CD42a + /CD14 + ，HLADR + /CD14 + and inflammatory cytokine levels in patients undergoing multilevel spinal fusion. Patients and methods Forty ASA I–II patients undergoing multilevel spinal fusion were randomly divided into Dex and control groups (n = 20). A continuous intravenous infusion of Dex (0.5 μg/kg/h) or normal saline was started 10 min prior to induction and was stopped 15 min before operation completion. Serum levels of CD42a + /CD14 + , HLADR + /CD14 + , WBC, PLT, CRP, IL-6, IL-10, and TNF-α were measured before induction (T 1 ), 30 min (T 2 ) after operation initiation, and 60 min (T 3 ), 1d (T 4 ), 3d (T 5 ), and 5d (T 6 ) post-operation. VAS values were obtained at T 3 , T 4 , T 5 and T 6 , as well as hospital days. Results: Treatment with Dex significantly decreased CD42a + /CD14 + at T 2 , T 3 , and T 4 , and markedly increased HLADR + /CD14 + at T 4 and T 5 when compared with controls. CRP and WBC were markedly decreased at T 2 , T 3 , T 4 and T 5 ( P 0.01 or P 0.05). Serum IL-6 and TNF-α level in Dex group was significantly increased at T 3 and T 4 ( P 0.05), and IL-6 and TNF-α level in control group was significantly increased at T 2 , T 3 , T 4 and T 5 ( P 0.05) when compared with their respective preoperative levels (T1). IL-6 and TNF-α levels at T 2 , T 3 , T 4 and T 5 in Dex group were significantly lower than those in control group ( P 0.05). There were no significant differences in operation time, hospital days or VAS values between the two groups ( P > 0.05). Conclusion: Dex can inhibit the inflammatory response and reduce immunosuppression in patients undergoing multilevel spinal fusion.

Purpose To evaluate the influence of preoperative inflammatory cytokine levels in the aqueous humor (AqH) on the endothelial cell density (ECD) after penetrating keratoplasty (PKP). Design Prospective, interventional, consecutive case series. Methods This study includes 70 consecutive patients (mean age 73.7 ± 10.6 years) who underwent PKP (37 eyes) or cataract surgery (controls, 33 eyes). A total of 70 AqH samples were collected at the beginning of each surgery. The levels of cytokines (interleukin [IL]-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon [IFN]-α, IFN-γ, monocyte chemotactic protein [MCP]-1, E-selectin and P-selectin) in AqH were measured by multiplex bead immunoassay. The subjects who underwent PKP were classified into 2 groups: ECD ≥ 1200 cells/mm 2 at 6 months (24 eyes), and ECD 2 at 6 months (13 eyes). Results The ECD at 3 months significantly correlated with the preoperative levels of IL-10 (r = −0.428, P = .02) and IFN-γ (r = −0.412, P = .029). The ECD at 6 months significantly correlated with the preoperative levels of IL-10 (r = −0.399, P = .024), MCP-1 (r = −0.444, P = .011), and IFN-γ (r = −0.474, P = .006). The preoperative levels of IL-6, IL-10, MCP-1, IFN-γ, and P-selectin in AqH were significantly higher in eyes with ECD 2 compared with those with ECD ≥ 1200 cells/mm 2 at 6 months ( P Conclusions Higher preoperative levels of IL-10, MCP-1, and IFN-γ in the AqH were associated with low ECD after PKP.

Prenatal exposure to influenza has previously been associated with increased risk of bipolar disorder (BD), an association that may be mediated by maternal cytokines. The objective of this study was to determine the association between maternal levels of cytokines measured during each trimester of pregnancy and the risk of BD in offspring. We conducted a case-control study nested in the Child Health and Development Study, a birth cohort that enrolled pregnant women in 1959-1966. Potential cases with DSM-IV-TR bipolar I disorder, bipolar II disorder, BD not otherwise specified, and BD with psychotic features were ascertained through electronic medical records, a public agency database, and a mailing to the cohort. Diagnoses were confirmed by clinical interview. Nine cytokines (IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and GM-CSF) were measured simultaneously by Luminex assays in archived prenatal maternal serum samples from 85 cases and 170 matched controls. Data were analyzed using conditional logistic regression. In the overall study sample, there were no significant associations between prenatal maternal cytokine levels and BD after adjustment for confounders. The risk of BD without psychotic features was decreased among subjects with higher maternal levels of first trimester log-transformed IL-4 (OR (95% CI)=0.76 (0.58, 0.98); p=0.04) and third trimester log-transformed IL-6 (OR (95% CI)=0.64 (0.42, 0.98); p=0.04). In conclusion, higher levels of prenatal maternal cytokines were not associated with increased risk for BD. Further studies with larger samples are necessary to confirm the finding.

Ketogenic diet is an effective treatment which has the potential to achieve a significant seizure reduction in drug-resistant epilepsy. The mechanism behind this effect is unclear, but one hypothesis is that the mechanism is anti-inflammatory. In this prospective study on pediatric patients we compared levels of cytokines and chemokines in the cerebrospinal fluid before and after three months on treatment to evaluate a possible anti-inflammatory effect. We analyzed 34 cytokines and chemokines in the cerebrospinal fluid of pediatric patients (n = 21) with refractory epilepsy by a multiplex assay. Beta-hydroxybutyric acid was measured in blood and cerebrospinal fluid. Seizure frequency in relation to diet treatment was assessed. For 9 different cytokines (CCL 7, CCL 21, CCL 22, CCL 25, CCL 27, IL-2, IL-10, CX3CL1 and MIF), a significant decrease ranging from 7 to 27% was seen after three months as compared to levels before the diet. In contrast, no cytokine displayed a significant increase during diet. A seizure reduction ≥ 50 % was seen in 15/21 patients (71 %) but no significant differences in cytokine decreases were found between responders and non-responders during treatment. A non-significant trend towards higher initial pre-treatment levels of cytokines was seen in responders, which were reduced following treatment. The levels of betahydroxybutyric acid were not related to seizure response. We conclude that while it is not possible to state a primary anti-inflammatory effect by dietary treatment from these data, an unequivocal immunological effect is seen and may be a part of the mechanism of ketogenic dietary treatment.

Objective Inflammation may play a role in the accelerated physical aging reported in schizophrenia, though biomarker findings and associations with demographic and clinical factors are inconsistent. Methods In a cross-sectional, case-control design, 95 outpatients with schizophrenia (mean age ± SD: 48.1 ± 10.2 years) and 95 demographically comparable healthy comparison subjects (HCs) (mean age ± SD: 48.1 ± 12.1 years) were studied. Sociodemographic and clinical data were collected, and plasma levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ) were assayed. The authors compared cytokine levels, examined demographic and clinical associations, and adjusted for relevant variables with linear models. Results Individuals with schizophrenia had higher levels of TNF-α and IL-6 but not IFN-γ than HCs. Age was not related to cytokine levels, and age relationships did not differ between diagnostic groups. Women had higher levels of IL-6. TNF-α and IL-6 levels were significantly correlated with depressive symptoms, and adjustment for depression reduced the group effect for both. Within the HCs, TNF-α levels were associated with physical comorbidity and body mass index. IL-6 levels were significantly correlated with body mass index and within schizophrenia patients, with worse mental and physical well-being. Accounting for physical morbidity and mental well-being reduced group differences in TNF-α and IL-6 levels, respectively. Worse positive symptoms were associated with higher IL-6 levels. Conclusion Higher TNF-α and IL-6 levels in schizophrenia patients were associated with depression, physical comorbidity, and mental well-being. Further longitudinal studies are warranted to assess inflammation as a potential treatment target for a subgroup of schizophrenia.

GM-CSF and G-CSF are widely used for their benefit in reducing chemotherapy-associated neutropenia. However, whether GM- or G-CSF administration could have tumorigenic or pro-metastatic effects or whether insulin resistance could negatively impact such effects is not known. Their ability to stimulate monocyte production at the same time with the highly sought after neutrophils' production, enables an enhanced potential for activation of tumor-associated macrophages. At the same time, IL-7 remains the main driver of B and T cell differentiation and maturation, a process linked to the development of insulin resistance and response to diabetes pharmacotherapy. Insulin secretagogues have the potential to interfere with the hematopoiesis process, respectively with the formation of lineages that may lead to a tumorigenic or pro-metastatic phenotype, but this relationship has not been yet investigated. The data presented here shows the relationship between pre-existing use of insulin secretagogues in women diagnosed with breast cancer and type 2 diabetes mellitus, the GM-CSF, G-CSF and IL-7 cytokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between investigated cytokines stratified by secretagogue use and controls, and interferon is also provided.

A growing body of evidence indicates that prenatal alcohol exposure (PAE) may predispose individuals to secondary medical disabilities later in life. Animal models of PAE reveal neuroimmune sequelae such as elevated brain astrocyte and microglial activation with corresponding region-specific changes in immune signaling molecules such as cytokines and chemokines. The aim of this study was to evaluate the effects of moderate PAE on the development and maintenance of allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in adult male rat offspring. Because CCI allodynia requires the actions of glial cytokines, we analyzed lumbar spinal cord glial and immune cell surface markers indicative of their activation levels, as well as sciatic nerve and dorsal root ganglia (DRG) cytokines in PAE offspring in adulthood. While PAE did not alter basal sensory thresholds before or after sham manipulations, PAE significantly potentiated adult onset and maintenance of allodynia. Microscopic analysis revealed exaggerated astrocyte and microglial activation, while flow cytometry data demonstrated increased proportions of immune cells with cell surface major histocompatibility complex II (MHCII) and β-integrin adhesion molecules, which are indicative of PAE-induced immune cell activation. Sciatic nerves from CCI rats revealed that PAE potentiated the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha (TNFα) protein levels with a simultaneous robust suppression of the anti-inflammatory cytokine, IL-10. A profound reduction in IL-10 expression in the DRG of PAE neuropathic rats was also observed. Taken together, our results provide novel insights into the vulnerability that PAE produces for adult-onset central nervous system (CNS) pathological conditions from peripheral nerve injury.

Periprosthetic joint infection is one of the most serious complications associated with arthroplasty surgery and poses great diagnostic difficulty. Traditional diagnostic methods used to diagnose infection in the lower extremity are less accurate for shoulder prosthetic joint infection due to the indolent nature of the most common pathogen, Propionibacterium acnes. In addition to preoperative lab work and intraoperative tissue cultures, a more recent tool for the evaluation of periprosthetic infection has been analysis of synovial fluid for antimicrobial peptides and cytokines. Investigation of synovial biomarkers such as α-defensin and interleukins offers improved ability to more accurately diagnose prosthetic shoulder joint infection.

Renin-angiotensin system has a role in inflammation and also involves in learning and memory. In the present study, the effects of captopril on lipopolysaccharide (LPS) induced learning and memory impairments, hippocampal cytokine levels and brain tissues oxidative damage was investigated.The rats were divided and treated : [1] saline (Control), [2] LPS (1mg/kg), [3-5] 10, 50 or 100mg/kg captopril 30min before LPS. The treatment was started since six days before the behavioral experiments and continued during the behavioral tests (LPS injection two h before each behavioral experiment).Administration of LPS prolonged the escape latency and traveled path to find the platform in Morris water maze (MWM) test (P0.01-P0.001) while, shortened the latency to enter the dark compartment in passive avoidance (PA) test (P0.001). Pretreatment by all doses of captopril improved performances of the rats in MWM (P0.05-P0.001) and also prolonged the latency to enter the dark in PA test (P0.001). LPS also increased IL-6, TNF-α, malondialdehyde (MDA) and nitric oxide(NO) metabolites in the hippocampal tissues (P0.05-P0.001) which were prevented by captopril (P0.05-P0.001). The thiol, superoxide dismutase(SOD) and catalase(CAT) in the hippocampus of LPS group were lower than the control (P0.001) while, they were enhanced when the aniamls were pretraeted by captopril (P0.01-P0.001).The results of present study showed that captopril improved the LPS-induced learning and memory impairments in rats which were accompanied with attenuating hippocampal cytokine levels and improving the brain tissues oxidative damage criteria.

Introduction Occupational exposure to Cadmium (Cd) may have serious health effect on workers. However, little is known about its effect on immune system. Moreover, previous studies have been inconclusive in stating the effect of Cd on immune system. The aim of our study was to estimate immune parameters in workers occupationally exposed to Cd. Material and methods 110 individuals occupationally exposed to Cd and 97 apparently healthy non-exposed individuals were recruited for this study. Blood Cadmium levels were determined by AAS. Lymphocyte subset were analyzed using flow cytometry and the cytokine levels were determined by ELISA. Results Exposed group have significantly higher levels of B-Cd. % of CD8 cells were higher in exposed while % of CD4 cells showed a decreasing trend in the exposed group. Among the CD3CD4 T cell subsets Th1 (%) and Tregs (%) cells were lower while Th17 (%) were higher in exposed group. Increased levels of IL-4 (Th2), IL-6 (Th2) and TNF- α (Th1) and decreased levels of IL-2 (Th1) and IL-10 (Tregs) were observed in Cd exposed workers which is indicative of a predominant pro-inflammatory response in Cd exposed workers. IL-17 (Th17) levels did not show any significant difference between the two groups. Increased Th17/Tregs ratio in the exposed group is also suggestive of an increased pro-inflammatory immune response in exposed group. Conclusion To conclude, even low level of exposure to Cd in occupational settings is associated with alterations in Th17 cells, which may further predispose an individual to other systemic abnormalities.

Objectives Few studies have investigated the distribution of multiple cytokines in fetal pleural effusion, and its clinical implications are uncertain. This study aimed to determine cytokine levels in fetal pleural effusion and their clinical role in affected fetuses. Methods We obtained fetal pleural fluid samples from 18 infants and investigated the profiles of 40 cytokines using multiplex immunoassay. Relationships among cytokines were estimated by Spearman correlation analysis. Possible associations of cytokine levels with fetal adverse outcomes, including perinatal demise and neurodevelopmental impairment, were studied using univariate logistic regression analysis. Results Several pro-inflammatory cytokines and CCL chemokines were highly correlated with each other. In contrast, CXCL chemokines had relatively weak correlations with other cytokines. The levels of IL-1β, IL-2, and CCL20 were significantly associated with the occurrence of fetal adverse outcomes. Based on our findings, IL-1β had the strongest causal link to adverse outcomes among the cytokines [odds ratio (OR): 19.74; 95% confidence interval (CI): 1.14–341.9; p = 0.040]. Conclusions Cytokine levels in fetal pleural effusion varied considerably among cases with or without adverse outcomes. These results provide important information for further clarifying the pathophysiology of fetal pleural effusion and a novel clinical implication that could predict the occurrence of adverse outcomes.

The present study aimed to verify the effects of caffeine supplementation on psychobiological parameters and its relationship with inflammatory cytokines in non-athlete subjects. We hypothesized that IL-10 may be responsible for the reduction in fatigue perception in response to caffeine supplementation. It was a randomized, double-blinded, cross-over, placebo-controlled study. Ten non-athlete subjects (26.9 ± 4.01 years old; 73.44 ± 9.57 kg; 15.94 ± 4.32 body fat kg) were evaluated. Sixty-min after caffeine (6 mg−1.kg−1 body mass) or placebo supplementation, high-intensity interval exercise test (1 min at 90% of Wmax and 2 min at 50% of Wmax) was performed to maximum voluntary exhaustion. Cytokine concentrations and psychobiological parameters were evaluated before (BE), immediately after (post-PE) and 1 h after exercise (1 h post-PE). We verify that IL-6 (0.35; 95% CI: 0.13 to 0.56; z = 3.24; p = 0.001; d = 1.14) and IL-10 (9.06; 95% CI 0.41 to 17.70; z = 2.05; p = 0.04; d = 1.12) increases post-PE in CAF group versus PLA group. Still, IL-10 levels were higher in CAF group 1 h post-PE (25.04; 95% CI: 8.95 to 41.31; z = 3.05; p = 0.002; d = 1.9) than PLA group. Moreover, 1 h post-PE vigor level was higher in the CAF group versus PLA group (4.53; 95% CI: 1.27 to 7.80; z = 2.72; p = 0.006; d = 0.46), and fatigue was lower in CAF group than PLA group (-5.08; 95% CI: −9.93 to −0.227; z = -2.05; p = 0.040; d = 0.67). We conclude that 1 h post-PE caffeine was able to decrease fatigue and increase vigor perception. IL-10 levels were higher 1 h post-PE in CAF group, suggesting, according to our hypothesis, that IL-10 may be associated with decrease fatigue perceptions after exercise.

Objective Our previous work has shown that, after intravitreal bevacizumab (IVB) administration, decreases in the levels of vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF), along with increases in the levels of interleukin (IL)-8 and transforming growth factor (TGF)-β 2 , can be observed. It is not yet known if similar changes occur after intravitreal ranibizumab (IVR). The purpose of this study was to examine intraocular cytokine changes after IVR. Design Prospective clinical study. Participants Subjects with proliferative diabetic retinopathy requiring pars plana vitrectomy (PPV) were recruited. Methods Participants received IVR as pre-treatment before PPV. Aqueous humour levels of IL-8, VEGF-A, PlGF, and TGF-β 2 were measured at time of pre-treatment and PPV. Results were analyzed using univariate statistical models. Results A total of 14 participants were recruited. After IVR administration, we observed a decrease in the levels of VEGF-A and PlGF, and an increase in the levels of IL-8 and TGF-β 2 . These results were statistically significant only for VEGF-A ( p = 0.0001) and IL-8 ( p = 0.0002). Conclusions The changes in cytokine levels after IVR mirror the changes seen after IVB. Further studies are warranted in order to determine if there are any differences between IVB and IVR in this regard. Objectif Nos travaux anterieurs ont montre que, suite a l'administration de bevacizumab intravitreen (BIV), on constate une diminution des niveaux de FCEA-A et du facteur de croissance placentaire (PlGF), et une augmentation des niveaux d'IL-8 et de TGF-β2. Nous ne savons pas encore si des changements similaires se produisent suite a l'administration de ranibizumab intravitreen (RIV). Le but de l'etude etait d'examiner les changements au niveau des cytokines intraoculaires apres l'administration de RIV. Nature Etude clinique prospective. Participants Nous avons recrute des sujets atteints de retinopathie diabetique proliferante (RDP) necessitant une vitrectomie par la pars plana (VPP). Methodes Les participants ont recu du RIV comme pretraitement avant de subir une VPP. Nous avons mesure le niveau d'humeur aqueuse de l'IL-8, du FCEA-A, du PlGF et du TGF-β2 au moment du pretraitement et de la VPP. Nous avons analyse les resultats a l'aide de modeles statistiques univaries. Resultats Au total, 14 participants ont ete recrutes. Apres l'administration du RIV, nous avons observe une diminution des niveaux de FCEA-A et de PlGF, et une augmentation des taux d'IL-8 et de TGF-β2. Nous n'avons constate des resultats statistiquement significatifs que pour le FCEA-A ( p = 0,0001) et l'IL-8 ( p = 0,0002). Conclusion Les changements au niveau des cytokines apres l'administration de RIV sont semblables aux changements observes apres l'administration de BIV. D'autres etudes sont necessaires afin de determiner s'il y a des differences entre le BIV et le RIV a cet egard.

OBJECTIVES: Obesity-induced, chronic, low-grade inflammation is involved in the pathogenesis of cardiovascular disease (CVD). Numerous spices have anti-inflammatory properties in animal models and humans. However, few studies have examined the anti-inflammatory effect of spices in the context of daily meal consumption, which is typically how spices are consumed. The objective of this study was to investigate the anti-inflammatory effect of chronic spice consumption in adults with overweight/obesity at risk for CVD. METHODS: Nonsmoking adults (30–75 years old) with overweight/obesity (BMI ≥ 25 and ≤ 35 kg/m(2)), elevated waist circumference (≥94 cm for men and ≥ 80 cm for women) and at least one other risk factor for CVD were recruited for a 3-period, crossover, randomized controlled-feeding study (n = 63). In random order, participants consumed an Average American Diet (AAD) for 4 weeks containing: 1) 0.6 g of spice blend per 2100 kcal, 2) 3.2 g of spice blend per 2100 kcal, or 3) 6.4 g of spice blend per 2100 kcal with a≥2-week washout period between each test period. The spice blend was comprised of 24 popular spices. Blood was collected at baseline and after each test period. Peripheral blood mononuclear cells were isolated, and the % of monocyte subsets (classical; CD14(++)CD16(−), intermediate; CD14(++)CD16(+), non-classical; CD14(+)CD16(++)) were quantified using flow cytometry. Plasma pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IL-8, MCP-1) were measured using ELISA. In a subset of participants (n = 6), transendothelial migratory function of each monocyte subset through MCP-1 stimulated human umbilical vein endothelial cells was evaluated. RESULTS: Plasma IL-6 was significantly reduced after consuming the AAD containing 3.2 g compared to 0.6 g of spice blend in men and postmenopausal women (P = 0.031). Transendothelial migration of classical monocytes was significantly reduced following consumption of the AAD containing 3.2 g and 6.4 g of the spice blend compared to 0.6 g of spice blend (P = 0.011). CONCLUSIONS: Consumption of an AAD with spices for 4 weeks attenuated inflammatory outcomes including plasma IL-6 and transendothelial migration of classical monocytes in adults with overweight/obesity. FUNDING SOURCES: McCormick Science Institute.

Objective To evaluate T-helper cytokine responses in a short-term high fat diet (HFD) induced impaired glucose metabolism. To further evaluate the modulation of T-helper 1 (Th1) and T-helper 2 (Th2) cytokines using short-term low-dose aspirin in combination with metformin. Design Two experiments were carried out in this study in order to evaluate the T-helper cytokine profiles in a state of impaired glucose metabolism. A total of 28 six-week-old male C57BL/6 mice were used in this study. In the first experiment, mice were fed either a high fat diet or low fat diet for a duration of 10 weeks. We then determined the Th1, Th2 and T-helper 17 (Th17) cytokine profiles. In the second experiment, we evaluated whether the short term 6-week treatment with low-dose aspirin in combination with metformin modulates T-helper cytokine profiles of the HFD-fed mice. Measurements In the first experiment, we measured the body weights, blood glucose levels, insulin levels, lipid profiles and haematological parameters. We further performed oral glucose tolerance testing following an 8-hour fast and serum Th1, Th2 and Th17 cytokine levels were also determined following short-term 8-week diet-feeding and 6-week low-dose aspirin and combined metformin with low-dose aspirin treatment. Results High fat diet-feeding caused a marked increase in circulating peripheral blood lymphocytes, which was attenuated by short-term low-dose aspirin treatment. Moreover, the HFD feeding resulted in 2-fold increase in total cholesterol and a 4-fold increase in low-density lipoprotein cholesterol when compared to the low-fat diet-fed group (p 0.05). While the combination of low-dose aspirin with metformin considerably reduced the levels of serum IFN-Ƴ (P Conclusion The early immunological and metabolic changes that occur in a state impaired glucose tolerance are accompanied by the increased production of Th2 cell cytokines. The short-term treatment using low-dose aspirin combined with metformin may provide therapeutic benefits in preventing complications associated with dysregulated Th2 cell responses.

Objective Kleine–Levin Syndrome (KLS) is a rare sleep disorder causing recurrent symptomatic episodes of severe hypersomnia, cognitive impairment, apathy, and derealization. These episodes are interspersed with long periods of normal sleep, cognition, and behavior. The pathogenesis of KLS is still unknown. The objective of this study was to determine serum cytokine levels in patients with KLS during and between episodes. Patients/Methods Fifty-two typical KLS patients were included in the study of whom 17 patients donated blood samples both during and between episodes. Blood samples were collected in USA, France, and Taiwan in a clinical setting. Processing of the samples was performed at the Stanford Center for Sleep Sciences and Medicine. Results We did not observe any changes in serum cytokine levels during KLS episodes compared to between episodes. In a small cohort of asymptomatic KLS patients and age- and gender matched healthy controls (n = 8/group) whose blood samples were all collected and processed at the same day; asymptomatic KLS patients had significantly higher levels of serum sVCAM1 cytokine compared to healthy controls. Conclusion These data suggest that KLS episodes are not accompanied by an abnormal systemic immune reaction.

Low-grade inflammation, measured by circulating levels of cytokines, is a pathogenic mechanism for several chronic diseases of aging. Identifying factors related to inflammation among African-American youths may yield insights into mechanisms underlying racial disparities in health. The purpose of the study was to determine whether (1) reported racial discrimination from ages 17-19 years forecasts heightened cytokine levels at the age of 22 years and (2) this association is lower for youths with positive racial identities.A longitudinal research design was used with a community sample of 160 African-Americans who were aged 17 years at the beginning of the study. Discrimination and racial identity were measured with questionnaires, and blood was drawn to measure basal cytokine levels. Ordinary least squares regression analyses were used to examine the hypotheses.After controlling for socioeconomic risk, life stress, depressive symptoms, and body mass index, racial discrimination (β = .307; p.01), racial identity (β = -.179; p.05), and their interaction (β = -.180; p.05) forecast cytokine levels. Youths exposed to high levels of racial discrimination evinced elevated cytokine levels 3 years later. This association was not significant for young adults with positive racial identities.High levels of interpersonal racial discrimination and the development of a positive racial identity operate jointly to determine low-grade inflammation levels that have been found to forecast chronic diseases of aging, such as coronary disease and stroke.

Background & aims Epicardial adipose tissue (EAT) is a source of a number of cytokines which could act in the pathogenesis of coronary artery disease (CAD). The potential relationship between known cardiovascular risk factors, such as smoking, dyslipidaemia or diabetes mellitus and EAT humoral signalling, has not been fully elucidated. Therefore, we designed and conducted a cross-sectional study to determine whether selected cardiovascular risk factors are linked to levels of cytokines in epicardial and subcutaneous adipose tissue (SAT). Methods Samples of SAT and EAT were collected from consecutive patients undergoing scheduled cardiac surgery. Tissue concentrations of tumour necrosis factor-ɑ (TNF-α), interleukin-6 (IL-6), adipocyte fatty acid-binding protein, leptin, and adiponectin were determined by ELISA. Results We enrolled 140 patients. TNF-α and IL-6 concentrations in EAT and SAT were significantly higher in current smokers (CS) than in never smokers (NS) and former smokers (FS). There were no differences between FS and NS. No other clinical variables were associated with cytokine concentrations in a regression analysis. Conclusions Smoking was independently associated with higher TNF-α and IL-6 concentrations in EAT and SAT. A novel observation that pro-inflammatory cytokines are elevated in EAT in smokers could contribute to identify potential mechanisms involved in the pathogenesis of adverse effects of tobacco smoking. There were no differences between EAT cytokine production in NS and FS, which support the importance of smoking cessation for cardiovascular risk reduction.