Search

Adipose-derived stem cells (ADSCs) comprise a promising therapy for osteoarthritis (OA). The therapeutic potential of ELIXCYTE®, an allogeneic human ADSC (hADSC) product, was demonstrated in a phase I/II OA clinical trial. However, the exact mechanism underlying such effects is not clear. Moreover, studies suggest that interleukin-11 (IL-11) has anti-inflammatory, tissue-regenerative, and immune-regulatory functions. Our aim was to unravel the mechanism associated with the therapeutic effects of ELIXCYTE® on OA and its relationship with IL-11. We cocultured ELIXCYTE® with normal human articular chondrocytes (NHACs) in synovial fluid obtained from individuals with OA (OA-SF) to investigate its effect on chondrocyte matrix synthesis and degradation and inflammation by assessing gene expression and cytokine levels. NHACs exposed to OA-SF exhibited increased MMP13 expression. However, coculturing ELIXCYTE® with chondrocytes in OA-SF reduced MMP13 expression in chondrocytes and downregulated PTGS2 and FGF2 expression in ELIXCYTE®. ELIXCYTE® treatment elevated anti-inflammatory cytokine (IL-1RA, IL-10, and IL-13) levels, and the reduction in MMP13 was positively correlated with IL-11 concentrations in OA-SF. These findings indicate that IL-11 in OA-SF might serve as a predictive biomarker for the ELIXCYTE® treatment response in OA, emphasizing the therapeutic potential of ELIXCYTE® to mitigate OA progression and provide insights into its immunomodulatory effects.

Autoimmune thyroid disease (AIT) is the most frequently linked autoimmune condition to type 1 diabetes (T1D). The analysis of immune profiles could provide valuable insights into the study of these diseases. This knowledge could play a crucial role in understanding the relationship between immune profiles and microcirculation structures and functions. The present study aimed to test the hypothesis that cytokine levels in T1D patients without and those with comorbid Hashimoto's disease differ significantly. The total study group (total T1D) consisted of 62 diabetic young patients: 43 T1D and 19 T1D + AIT matched for age, age at onset, and duration of diabetes. The control group consisted of 32 healthy young subjects. The levels of cytokines (including TNF-α, IL-35, IL-4, IL-10, IL-18, IL-12, VEGF, and angiogenin) were quantified throughout this investigation. A comparative assessment of the cytokines profiles between the control group and total T1D revealed a statistically significant elevation in the levels of IL-4, TNF-α, IL-18, VEGF, and angiogenin, accompanied by a notable decline in IL-10. However, IL-35 and IL-12 exhibited comparable levels between the two groups. A comparison of cytokine levels between T1D + AIT and T1D groups revealed that only angiogenin levels were statistically significantly higher in T1D + AIT. The results of our study indicated that the alterations in cytokine levels associated with AIT did not correspond to the observed changes in T1D-related outcomes. The sole notable observation was the elevation of angiogenin expression, an angiogenic factor. [ABSTRACT FROM AUTHOR]

Introduction: The release of pro-inflammatory cytokines in critically ill patients with sepsis leads to endothelial dysfunction resulting in cardiocirculatory insufficiency. Their extracorporeal elimination using the cytokine adsorber CytoSorb® (CS) (adsorption of especially hydrophobic molecules < 60 kDa) might be promising, but data about the adsorption capacity as well as a potential harmful adsorption of anti-inflammatory cytokines are missing so far. Methods: The prospective Cyto-SOLVE-study included 15 patients with sepsis or other hyperinflammatory conditions (interleukin 6 > 500 pg/ml), continuous kidney replacement therapy, and the application of CS. Various cytokines and chemokines were measured pre- and post-CS as well as in patients' blood at predefined timepoints. Significant changes in the concentrations were detected with the Wilcoxon test with associated samples. Clearance of the adsorber (ml/min) was calculated with: b l o o d f l o w ∗ c o n c e n t r a t i o n p r e - p o s t c o n c e n t r a t i o n pre . Results: Most of the inflammatory mediators showed a high initial extracorporeal clearance of 70–100 ml/min after CS installation, which dropped quickly to 10-30 ml/min after 6 h of treatment. No difference in clearance was observed between pro- and anti-inflammatory cytokines. Despite extracorporeal adsorption, a significant (p < 0.05) decrease in the blood concentration after 6 h was only observed for the pro-inflammatory cytokines tumor necrosis factorα (TNF-α) (median 284 vs. 230 pg/ml), vascular endothelial growth factor (VEGF) (median 294 vs. 252 pg/ml), macrophage inflammatory protein 1a (MIP-1a) (median 11.1 vs. 9.0 pg/ml), and regulated upon activation, normal T cell expressed and secreted (RANTES) (median 811 vs. 487 pg/ml) as well as the anti-inflammatory cytokines interleukin 4 (median 9.3 vs. 6.4 pg/ml), interleukin 10 (median 88 vs. 56 pg/ml), and platelet-derived growth factor (PDGF) (median 177 vs. 104 pg/ml). A significant (p < 0.05) decrease in patients' blood after 12 h was only detected for interleukin 10. Conclusions: CS can adsorb pro- as well as anti-inflammatory mediators with no relevant difference regarding the adsorption rate. A fast saturation of the adsorber resulted in a rapid decrease of the clearance. The potential clinical benefit or harm of this unspecific cytokine adsorption needs to be evaluated in the future. Trial Registration: ClinicalTrials.gov NCT04913298, registration date June 4, 2021. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB), though the underlying mechanisms linking DM and TB remain ambiguous. Macrophages are a key player in the innate immune response and their phagocytic ability is enhanced in response to microbial infections. Upon infection or inflammation, they also repel invading pathogens by generating; reactive oxygen species (ROS), reactive nitrogen species (RNS), pro-inflammatory cytokines (IL-1β and IL-6), and anti-inflammatory cytokines (IL-10). However, the robustness of these innate defensive capabilities of macrophages when exposed to hyperglycemia remains unclear. In our current work, we explored the production of these host defense molecules in response to challenge with Mycobacterium tuberculosis (Mtb) infection and lipopolysaccharide (LPS) stimulation. Utilizing peritoneal macrophages from high-fat diet + streptozotocin induced diabetic mice and hyperglycemic THP-1-derived macrophages as model systems; we found that LPS stimulation and Mtb infection were ineffective in stimulating the production of ROS, RNS, and pro-inflammatory cytokines in cells exposed to hyperglycemia. On the contrary, an increase in production of anti-inflammatory cytokines was observed. To confirm the mechanism of decreased anti-bacterial activity of the diabetic macrophage, we explored activation status of these compromised macrophages and found decreased surface expression of activation (TLR-4) and differentiation markers (CD11b and CD11c). We postulate that this could be the cause for higher susceptibility for Mtb infection among diabetic individuals. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a common disorder caused by immune system dysregulation. The present contribution describes a randomized, double-blind, placebo-controlled comparative evaluation of the influence of a unique food-grade co-delivery form of curcumin and ashwagandha extracts (CQAB) in comparison to a bioavailable curcumin formulation (CGM) and placebo employing healthy participants, (n = 96), characterized with mild AR. The subjective measurements (TNSS, BIS and POMS-SF questionnaires) clearly demonstrated the efficacy of CQAB over CGM in the alleviation of AR symptoms and hence the quality of life. Further, CQAB administration also showed significant modulation of biochemical parameters (significant decrease in Th2 cytokines, pro-inflammatory cytokines, CD4+/CD8+ ratio and IgE, and a significant increase in Th1 cytokines, anti-inflammatory cytokine IL-10 as well as for the immunoglobulins IgG, IgM, and IgA) in support of its improved immune-balancing effect, compared to CGM. Both CQAB and CGM were well tolerated without any adverse events.

(1) Background: Patients with Fuchs' endothelial corneal dystrophy (FECD) may have coexisting cataracts and, therefore, may require a cataract surgery, which poses challenges due to potential endothelial cell damage. FECD is a degenerative eye disease of unclear etiology, with inflammatory cytokines maybe playing an important role in its development and progression. The present study aimed to investigate the cytokine profile in the aqueous humor of FECD eyes with cataract. (2) Methods: Fifty-two patients were included in the study, 26 with FECD + cataract and 26 with cataract as a control group. Samples of the aqueous humor were analyzed for pro- and anti-inflammatory cytokines using a Bio-Plex 200 system. (3) Results: Interleukin 1 receptor antagonist (IL-1Ra) and interleukin IL-8 levels were significantly higher in the aqueous humor of FECD + cataract patients compared to the control/cataract group. Moreover, the levels of anti-inflammatory IL-10 showed a strong trend to be higher in the FECD + cataract group compared to the control group. In contrast, there were no statistically significant differences in IL-1β, IL-6, IL-4, IL-10, IL-13, IL-17A, and tumor necrosis factor TNF-α between the groups. (4) Conclusions: Presented research contributes to a better understanding of FECD pathogenesis. Elevated levels of IL-1Ra and IL-8 may serve as a defense mechanism in people with FECD and coexisting cataract. [ABSTRACT FROM AUTHOR]

Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsingremitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF. This study aimed to investigate the effect of DMF administration in the gut draining lymph nodes cells of C57BL6/J female mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have demonstrated that the treatment with DMF (7.5 mg/kg) significantly reduces the severity of EAE. This reduction of the severity is accompanied by the increase of both proinflammatory and anti-inflammatory mechanisms at the beginning of the treatment. As the treatment progressed, we observed an increasing number of regulatory Foxp3 negative CD4 T cells (Tr1), and anti-inflammatory cytokines such as IL-27, as well as the reduction of PGE2 level in the mesenteric lymph nodes of mice with EAE. We provide evidence that DMF induces a gradual antiinflammatory response in the gut draining lymph nodes, which might contribute to the reduction of both intestinal discomfort and the inflammatory response of EAE. These findings indicate that the gut is the first microenvironment of action of DMF, which may contribute to its effects of reducing disease severity in MS patients. [ABSTRACT FROM AUTHOR]

Oligodendrocyte progenitor cells (OPCs) were regarded for years solely for their regenerative role; however, their immune‐modulatory roles have gained much attention recently, particularly in the context of multiple sclerosis (MS). Despite extensive studies on OPCs, there are limited data elucidating the interactions between their intrinsic regenerative and immune functions, as well as their relationship with the inflamed central nervous system (CNS) environment, a key factor in MS pathology. We examined the effects of pro‐inflammatory cytokines, represented by interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α, as well as anti‐inflammatory cytokines, represented by interleukin (IL)‐4 and IL‐10, on OPC differentiation and immune characteristics. Using primary cultures, enzyme‐linked immunosorbent assay and immunofluorescence stainings, we assessed differentiation capacity, phagocytic activity, major histocompatibility complex (MHC)‐II expression, and cytokine secretion. We observed that the anti‐inflammatory milieu (IL4 and IL10) reduced both OPC differentiation and immune functions. Conversely, exposure to TNF‐α led to intact differentiation, increased phagocytic activity, high levels of MHC‐II expression, and cytokines secretion. Those effects were attributed to signalling via TNF‐receptor‐2 and counteracted the detrimental effects of IFN‐γ on OPC differentiation. Our findings suggest that a pro‐regenerative, permissive inflammatory environment is needed for OPCs to execute both regenerative and immune‐modulatory functions. [ABSTRACT FROM AUTHOR]

Abstract Background The treatment of diverse diseases using plant-derived products is actively encouraged. In the past few years, cannabidiol (CBD) has emerged as a potent cannabis-derived drug capable of managing various debilitating neurological infections, diseases, and their associated complications. CBD has demonstrated anti-inflammatory and curative effects in neuropathological conditions, and it exhibits therapeutic, apoptotic, anxiolytic, and neuroprotective properties. However, more information on the reactions and ability of CBD to alleviate brain-related disorders and the neuroinflammation that accompanies them is needed. Main body This narrative review deliberates on the therapeutic and remedial prospects of CBD with an emphasis on neurological and neuropsychiatric disorders. An extensive literature search followed several scoping searches on available online databases such as PubMed, Web of Science, and Scopus with the main keywords: CBD, pro-inflammatory cytokines, and cannabinoids. After a purposive screening of the retrieved papers, 170 (41%) of the articles (published in English) aligned with the objective of this study and retained for inclusion. Conclusion CBD is an antagonist against pro-inflammatory cytokines and the cytokine storm associated with neurological infections/disorders. CBD regulates adenosine/oxidative stress and aids the downregulation of TNF-α, restoration of BDNF mRNA expression, and recovery of serotonin levels. Thus, CBD is involved in immune suppression and anti-inflammation. Understanding the metabolites associated with response to CBD is imperative to understand the phenotype. We propose that metabolomics will be the next scientific frontier that will reveal novel information on CBD’s therapeutic tendencies in neurological/neuropsychiatric disorders.

Abstract Background Chronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system. Non-pharmacologic interventions have received increasing attention as potential strategies to alleviate chronic low back pain and improve patient outcomes. The aim of this systematic review was to comprehensively assess the changes in blood inflammatory biomarkers after non-pharmacologic interventions for CLBP patients, thus trying to understand the complex interactions between non-pharmacologic interventions and inflammatory biomarker changes in CLBP. Methods A thorough search (from January 1st, 2002 to October 5th, 2022) of PubMed, Medline (platform Web of Science), and the Cochrane Library (platform Wiley Online Library) were conducted, and inclusion criteria as well as exclusion criteria were refined to selection of the studies. Rigorous assessments of study quality were performed using RoB 2 from Cochrane or an adaptation of the Downs and Black checklist. Data synthesis includes alterations in inflammatory biomarkers after various non-pharmacologic interventions, including exercise, acupressure, neuro-emotional technique, and other modalities. Results Thirteen primary studies were included in this systematic review, eight randomized controlled trials, one quasi-randomized trial, and four before-after studies. The interventions studied consisted of osteopathic manual treatment (one study), spinal manipulative therapy (SMT) (three studies), exercise (two studies), yoga (two studies) and acupressure (two studies), neuro-emotional technique (one study), mindfulness-based (one study) and balneotherapy study (one study). Four studies reported some changes in the inflammatory biomarkers compared to the control group. Decreased tumor necrosis factor-alpha (TNF-α) after osteopathic manual treatment (OMT), neuro-emotional technique (NET), and yoga. Decreased interleukin (IL)-1, IL-6, IL-10, and c-reactive protein (CRP) after NET, and increased IL-4 after acupressure. Another five studies found changes in inflammatory biomarkers through pre- and post-intervention comparisons, indicating improvement outcomes after intervention. Increased IL-10 after balneotherapy; decreased TNF-α, IL-1β, IL-8, Interferon-gamma, interferon-γ-induced protein 10-γ-induced protein 10 after exercise; decreased IL-6 after exercise and SMT; decreased CRP and chemokine ligand 3 after SMT. Conclusion Results suggest a moderation of inflammatory biomarkers due to different non-pharmacologic interventions for CLBP, generally resulting in decreased pro-inflammatory markers such as TNF-α and IL-6 as well as increased anti-inflammatory markers such as IL-4, thus revealing the inhibition of inflammatory processes by different non-pharmacologic interventions. However, a limited number of high-quality studies evaluating similar interventions and similar biomarkers limits the conclusion of this review.

Metabolic memory refers to the long-term effects of achieving early glycemic control and the adverse implications of high blood glucose levels, including the development and progression of diabetes complications. Our study aimed to investigate whether the phenomenon of metabolic memory plays a role in the immune profile of young patients with uncomplicated type 1 diabetes (T1D). The study group included 67 patients with uncomplicated type 1 diabetes with a mean age of 15.1 ± 2.3 years and a minimum disease duration of 1.2 years. The control group consisted of 27 healthy children and adolescents with a mean age of 15.1 ± 2.3 years. Patients were divided into three groups according to their HbA1c levels at the onset of T1D, and the average HbA1c levels after one and two years of disease duration. The subgroup A1 had the lowest initial HbA1c values, while the subgroup C had the highest initial HbA1c values. Cytokine levels (including TNF-α, IL-35, IL-4, IL-10, IL-18, and IL-12) were measured in all study participants. Our data analysis showed that subgroup A1 was characterized by significantly higher levels of IL-35 and IL-10 compared to all other groups, and significantly higher levels of IL-4 compared to group B. Additionally, a comparative analysis of cytokine levels between the groups of diabetic patients and healthy controls demonstrated that subgroup A1 had significantly higher levels of anti-inflammatory cytokines. The lipid profile was also significantly better in subgroup A1 compared to all other patient groups. Based on our findings, it appears that an inflammatory process, characterized by an imbalance between the pro- and anti-inflammatory cytokines, is associated with poor glycemic control at the onset of diabetes and during the first year of disease duration. These findings also suggest that both metabolic memory and inflammation contribute to the abnormal lipid profile in patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis is a chronic immune-mediated inflammatory bowel disease that involves inflammation and ulcers of the colon and rectum. To date, no definite cure for this disease is available. Objective: The objective of the current study was to assess the effect of Calliandra haematocephala on inflammatory mediators and oxidative stress markers for the exploration of its anti-ulcerative colitis activity in rat models of acetic acid-induced ulcerative colitis. Methods: Methanolic and n-hexane extracts of areal parts of the plant were prepared by cold extraction method. Phytochemical analysis of both extracts was performed by qualitative analysis, quantitative methods, and high-performance liquid chromatography (HPLC). Prednisone at 2 mg/kg dose and plant extracts at 250, 500, and 750 mg/kg doses were given to Wistar rats for 11 days, which were given acetic acid on 8th day through the trans-rectal route for the induction of ulcerative colitis. A comparison of treatment groups was done with a normal control group and a colitis control group. To evaluate the anti-ulcerative colitis activity of Calliandra haematocephala, different parameters such as colon macroscopic damage, ulcer index, oxidative stress markers, histopathological examination, and mRNA expression of pro and anti-inflammatory mediators were evaluated. mRNA expression analysis was carried out by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Results: The phytochemical evaluation revealed polyphenols, flavonoids, tannins, alkaloids, and sterols in both extracts of the plant. Results of the present study exhibited that both extracts attenuated the large bowel inflammation and prevented colon ulceration at all tested doses. Macroscopic damage and ulcer scoreswere significantly decreased by both extracts. Malondialdehyde (MDA) levels and nitrite/nitrate concentrations in colon tissues were returned to normal levels while superoxide dismutase (SOD) activity was significantly improved by all doses. Histopathological examination exhibited that both extracts prevented the inflammatory changes, cellular infiltration, and colon thickening. Gene expression analysis by RT-qPCR revealed the downregulation of pro-inflammatory markers such as tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) whereas the anti-inflammatory cytokines including Interleukin-4 (IL-4) and Interleukin-10 (IL-10) were found to be upregulated in treated rats. Conclusion: It was concluded based on study outcomes that methanolic and n-hexane extracts of Calliandra haematocephala exhibited anti-ulcerative colitis activity through modulation of antioxidant defense mechanisms and the immune system. In this context, C. haematocephala can be considered as a potential therapeutic approach for cure of ulcerative colitis after bioassay-directed isolation of bioactive phytochemicals and clinical evaluation. [ABSTRACT FROM AUTHOR]

Endometriosis is a chronic inflammatory disease, which explains the pain that such patients report. Currently, we are faced with ineffective, non-invasive diagnostic methods and treatments that come with multiple side effects and high recurrence rates for both the disease and pain. These are the reasons why we are exploring the possibility of the involvement of pro-inflammatory and anti-inflammatory molecules in the process of the appearance of endometriosis. Cytokines play an important role in the progression of endometriosis, influencing cell proliferation and differentiation. Pro-inflammatory molecules are found in intrafollicular fluid. They have an impact on the number of mature and optimal-quality oocytes. Endometriosis affects fertility, and the involvement of endometriosis in embryo transfer during in vitro fertilization (IVF) is being investigated in several studies. Furthermore, the reciprocal influence between anti-inflammatory and pro-inflammatory cytokines and their role in the pathogenesis of endometriosis has been assessed. Today, we can affirm that pro-inflammatory and anti-inflammatory cytokines play roles in survival, growth, differentiation, invasion, angiogenesis, and immune escape, which provides a perspective for approaching future clinical implications and can be used as biomarkers or therapy. [ABSTRACT FROM AUTHOR]

Pulmonary disease represents a substantial global health burden. Increased air pollution, especially fine particulate matter (PM2.5) is the most concerned proportion of air pollutants to respiratory health. PM2.5 may carry or combine with other toxic allergens and heavy metals, resulting in serious respiratory allergies and anaphylactic reactions in the host. Available treatment options such as antihistamines, steroids, and avoiding allergens/dust/pollutants could be limited due to certain side effects and immense exposure to air pollutants, especially in most polluted countries. In this mini-review, we summarized how PM2.5 triggers respiratory hyperresponsiveness and inflammation, and the probiotic Lactiplantibacillus plantarum supplementation could minimize the risk of the same. L. plantarum may confer beneficial effects in PM2.5-associated pulmonary inflammation due to significant antioxidant potential. We discussed L. plantarum's effect on PM2.5-induced reactive oxygen species (ROS), inflammatory cytokines, lipid peroxidation, and DNA damage. Available preclinical evidence shows L. plantarum induces gut-lung axis, SCFA, GABA, and other neurotransmitter signaling via gut microbiota modulation. SCFA signals are important in maintaining lung homeostasis and regulating intracellular defense mechanisms in alveolar cells. However, significant research is needed in this direction to contemplate L. plantarum's therapeutic potential in pulmonary allergies. [ABSTRACT FROM AUTHOR]

Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsing-remitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF. This study aimed to investigate the effect of DMF administration in the gut draining lymph nodes cells of C57BL6/J female mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have demonstrated that the treatment with DMF (7.5 mg/kg) significantly reduces the severity of EAE. This reduction of the severity is accompanied by the increase of both proinflammatory and anti-inflammatory mechanisms at the beginning of the treatment. As the treatment progressed, we observed an increasing number of regulatory Foxp3 negative CD4 T cells (Tr1), and anti-inflammatory cytokines such as IL-27, as well as the reduction of PGE2 level in the mesenteric lymph nodes of mice with EAE. We provide evidence that DMF induces a gradual anti-inflammatory response in the gut draining lymph nodes, which might contribute to the reduction of both intestinal discomfort and the inflammatory response of EAE. These findings indicate that the gut is the first microenvironment of action of DMF, which may contribute to its effects of reducing disease severity in MS patients.

Background. Burn wound healing is recognized as a complex process involving synergetic interactions between different cells, cytokines and growth factors. The adverse interactions can underlie chronicization of the process. Accordingly, the paper presents a relevant study into mechanisms of natural wound dressings, capable of influencing the processes of inflammation, angiogenesis, and skin resurfacing.Objective. To carry out a comparative evaluation of efficiency of burn wound healing with derma-based hydrogel according to the dynamics of proand anti-inflammatory factors.Methods. Development of a hydrogel material involved dermis samples of Landrace breed of pig, subjected to partial alkaline hydrolysis. In order to carry out a comparative evaluation of burn wound healing efficiency, the authors simulated direct thermal injury in three groups of sphinx (hairless) rats: group 1 (control group) — rats without treatment (n = 20), group 2 (comparison group) — rats treated with Levomekol ointment (n = 20), and group 3 (experimental group) — rats treated with hydrogel material (n = 20). Before and after injuring on days 1, 3, 7, 14, the content of cytokines interleukin-1β, interleukin-4, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α by enzyme immunoassay. The wound samples were explanted for histological examination on days 3, 7 and 14 after the beginning of the experiment. Statistical processing of the obtained results on DNA content in hydrogel, cytokine content in serum and morphometric data was performed using GraphPadPrism 6.04, Microsoft Excel 2016 (Microsoft, USA).Results. When determining the content dynamics of nonspecific markers of inflammation, an increase in the concentrations of interleukin-1β and tumor necrosis factor-α on day 1 after the hydrogel application was recorded, as well as an increase in interleukin-6 on days 3 and 7, while the concentrations of interleukin-8 did not change significantly throughout the experiment. Thus, dermal components are indicated to participate in the inhibition of acute-phase immune reactions. With regard to anti-inflammatory factors, the study revealed a decrease in the concentration of interleukin-10 on days 1 and 7, an increase in interleukin-4 on day 3 as compared to the control group, thereby indicating a pronounced anti-inflammatory effect and prolonged action of the hydrogel.Conclusion. Comparative analysis of the pro-inflammatory cytokines levels (interleukin-1β, interleukin-8) showed pronounced anti-inflammatory effects of the derma-based hydrogel material. Introduction of exogenous biological components of the extracellular matrix (collagen and its hydrolysates) had a significant influence on the regulation of anti-inflammatory cytokines synthesis, presumably contributing to faster successful epithelization and wound healing.

The most important role in homeostasis of intestinal immune belongs to the immunoregulatory properties of the microbiota which activates intracellular signaling systems, cytokine expression, production of protective factors and limits inflammatory reactions in the intestine by interacting with the pattern recognition receptors. The outcome of interactions between the microbiota and host cells (development of an inflammatory process or maintenance of intestinal homeostasis) depends on many factors, including a potential ability of intestinal commensals to influence the cytokine network in human body. Due to disturbances of quantitative and qualitative microbiota profile (dysbiosis), the cytokine balance may be changed by the influence of intestinal microsymbionts and their metabolites on immune and epithelial cells of intestines, thus contributing to the development of various human disorders. The aim of this study was to evaluate the immunoregulatory properties of eubiotic and dysbiotic human intestinal microsymbionts by assessing the effects of their cell-free supernatants on cytokine production in the in vitro system. The study was conducted on 49 eubiotic and 77 dysbiotic strains of microorganisms isolated from conditionally healthy patients examined for colon dysbiosis. To assess immunoregulatory properties of intestinal microsymbionts, we studied the effects of cell-free supernatants from bacterial and fungal cultures up on production of proinflammatory (IFNγ, TNFα, IL-17, IL-8, IL-6) and anti-inflammatory (IL-10, IL-1ra) cytokines secreted by mononuclear cells isolated from peripheral blood of healthy persons. The intestinal microbiota was determined by bacteriological methods. Identification of isolated microbial cultures was performed using MALDI TOF MS Microflex LT series (Bruker Daltonics, Germany). The level of cytokines was determined by enzyme immunoassay using commercial test systems (“Cytokine”, Russia). Statistical evaluation included discriminant analysis, classification decision tree and resultant mapping method. The multivariate statistical analysis enabled us to determine the range of the most informative indexes among cytokines and microbial cultures that changing their production in order to assess the state of homeostasis in eubiosis and intestinal dysbiosis. It was found that the supernatants of eubiotic cultures of intestinal symbionts exhibited a pronounced ability to inhibit the level of pro-inflammatory cytokines (IFNγ, IL-8) and to stimulate the secretion of anti-inflammatory cytokine (IL-10), whereas the dysbiotic cultures predominantly induced pro-inflammatory cytokines (IL-17, IFNγ, TNFα). In maintaining a uniform balance between pro- and anti-inflammatory cytokines during eubiosis, both associations of microsymbionts (in descending order of factor loads): Bacteroides spp. > E. coli > Lactobacillus spp.), and monocultures (Bifidobacterium spp. and Lactobacillus spp.) made a significant contribution via IL-10 induction. In cases of intestinal dysbiosis, we found an increased number of associations between microsymbionts inducing secretion of pro-inflammatory cytokines was. The pro-inflammatory profile of dysbiotic cultures was determined by the influence on IFNγ production (ranged in descending order of factor loads) of Bifidobacterium spp. > Enterococcus spp. > E. coli > Lactobacillus spp. associations, as well as S. aureus > Candida spp associations. The secretion of IL-17 was influenced by the monoculture of Clostridium spp., and by association C. acnes > S. aureus > Klebsiella spp. Monocultures of Bifidobacteria and Escherichia exerted effects upon TNFα production. Thus, during eubiotic state, the normobiota maintains a uniform balance of pro- and anti-inflammatory cytokines, and, in presence of intestinal dysbiosis, a shift in the balance of cytokines towards pro-inflammatory ones may occur due to increased levels of their secretion, an expanded spectrum of cytokines from this group, and increased number of single bacteria and associations of microbial cultures affecting their production.

Abstract Background Severe malaria (SM) is a fatal multi-system disease which accounted for an estimated 619,000 deaths in 2021. Less than 30% of children presenting with SM are diagnosed and treated promptly, resulting in increased mortality and neurologic impairments in survivors. Studies have identified cytokine profiles that differentiate the various clinical manifestations of malaria (severe and uncomplicated). However, the diagnostic capability of these cytokines in differentiating between the disease states in terms of cut-off values has not yet been determined. Methods The plasma levels of 22 pro-inflammatory cytokines (Eotaxin/CCL 11, interferon-gamma (IFN-γ), interleukin (IL)- 2, IL-6, IL-1β, IL-12p40/p70, IL-17A, RANTES, MCP-1, IL-15, IL-5, IL-1RA, IL-2R, IFN-α, IP-10, TNF, MIG, MIP-1α, MIP-1β, IL-7, IL-8 and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), and 3 anti-inflammatory cytokines-(IL-4, IL-13 and IL-10) in patients with SM, uncomplicated malaria (UM) and other febrile conditions, were measured and compared using the Human Cytokine Magnetic 25-Plex Panel. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of these cytokines. Results The level of the pro-inflammatory cytokine, IL-17A, was significantly higher in the SM group as compared to the UM group. Levels of the anti-inflammatory cytokines however did not differ significantly among the SM and UM groups. Only IL-1β and IL-17A showed good diagnostic potential after ROC curve analysis. Conclusion The data show that levels of pro-inflammatory cytokines correlate with malaria disease severity. IL-1β and IL-17A showed good diagnostic potentials and can be considered for use in clinical practice to target treatment.

Because of evident role of renin–angiotensin system in the etiology of rheumatoid arthritis, the current study's objective was to assess the anti-arthritic efficacy of ramipril through CFA-instigated arthritic model. The drug has been shown to have anti-inflammatory potential. CFA-instigated arthritic model assessed the anti-arthritic efficacy of ramipril by estimating different parameters, including paw volume, arthritic index scoring, haematological and biochemical attributes, histological and radiographic analyses, and various cytokines level. Ramipril significantly (p < 0.001) reduced paw volume and the arthritic index especially at the dose of 4mg/kg. The biochemical and haematological changes were likewise restored to normal by ramipril administration with an increase in anti-inflammatory cytokines while reducing pro-inflammatory cytokines level. Ramipril's ability to prevent arthritis by preserving the normal architecture of arthritis-induced joints is further supported by radiographic and histological investigation. The study's findings demonstrated ramipril's considerable anti-arthritic activity. To identify the precise mechanism of action, however, thorough mechanistic studies are still needed. [ABSTRACT FROM AUTHOR]

• Serum IL-41 concentrations were significantly elevated in HUA patients. • The area under the ROC curve (AUC) for IL-41 in HUA patients was 0.7443, while the AUC for IL-41 combined with the platelet count was 0.8109. • Circulating IL-41 level was positively correlated with age. • IL-41 may be a potential diagnostic biomarker of HUA. Interleukin (IL)-41 is a recently discovered secreted protein that is expressed in a variety of tissues, and it is associated with several immune and metabolic diseases. However, IL-41 has not been studied in hyperuricemia (HUA). Forty-four HUA patients and 44 healthy controls (HCs) were included in this study, and we collected theirgeneral and biochemical parameters, including white blood cell, neutrophil, lymphocyte, and platelet counts, mean platelet volume, platelet distribution width, serum creatinine, blood urea nitrogen, fasting blood glucose, total triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, total protein, albumin, alkaline phosphatase, gamma-glutamyltransferase, and hemoglobin concentration. The level of serum IL-41 was determined using an enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was exploited to identify the independent risk factors associated with HUA, and the clinical diagnostic value of IL-41 was analyzed by applying the receiver operating characteristic (ROC) curve. We assessed the association between IL-41 and clinical parameters with Spearman's rank correlation. Circulating IL-41 levels were significantly higher in HUA patients than in the HCs group (460.3 pg/mL vs. 261.3 pg/mL, respectively; P < 0.001). The area under the ROC curve (AUC) for IL-41 in HUA patients was 0.7443 (with a cut-off value of 311.055 pg/mL, a sensitivity of 68.18 %, and a specificity of 72.73 %), while the AUC for IL-41 combined with the platelet count was 0.8109. Correlation analysis revealed that the circulating IL-41 level was positively correlated with age in HCs and HUA patients. We herein demonstrated that serum IL-41 was elevated in HUA patients and that it may constitute a novel biomarker of anti-inflammatory response related to HUA. [ABSTRACT FROM AUTHOR]

Simple Summary: Soluble factors, the cytokines, influence the ability of an individual host defense against intruders, e.g., the SARS-CoV-2 virus. Distinct T cells are a major source of many of those molecules. The helper T cells are divided into categories according to their action on the immune response: the more pro-inflammatory helper T cells 1 (Th1: TNF-α, IFN-γ), the anti-inflammatory (Th2: IL-10) cells, and the more regulatory Th17 (IL-17, TGF-β1) and Treg (TGF-β1) cells. In the present report, we elaborate on the genetically determined activity of such cytokines, regarding defined polymorphisms with known impact on the cytokine expression and their influence on the course of SARS-CoV-2 infection. We selected from a larger cohort individuals from the same household (n = 58). We divided them into households with all individuals SARS-CoV-2-PCR positive (n = 29) with 61 individuals, mixed households (n = 24) with 62 individuals and households (n = 5) with 15 SARS-CoV-2-negative individuals and compared the frequency of distinct polymorphisms. The results obtained indicate a role for a genetically determined balance of the different T helper cell pathways. We addressed the question of the influence of the molecular polymorphism of cytokines from different T helper subsets on the susceptibility to SARS-CoV-2 infection. From a cohort of 527 samples (collected from 26 May 2020 to 31 March 2022), we focused on individuals living in the same household (n = 58) with the SARS-CoV-2-infected person. We divided them into households with all individuals SARS-CoV-2 PCR positive (n = 29, households, 61 individuals), households with mixed PCR pattern (n = 24, 62) and negative households (n = 5, 15), respectively. TGF-β1 and IL-6 were the only cytokines tested with a significant difference between the cohorts. We observed a shift toward Th2 and the regulatory Th17 and Treg subset regulation for households with all members infected compared to those without infection. These data indicate that the genetically determined balance between the cytokines acting on different T helper cell subsets may play a pivotal role in transmission of and susceptibility to SARS-CoV-2 infection. Contacts infected by their index persons were more likely to highly express TGF-β1, indicating a reduced inflammatory response. Those not infected after contact had a polymorphism leading to a higher IL-6 expression. IL-6 acts in innate immunity, allergy and on the T helper cell differentiation, explaining the reduced susceptibility to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Green coffee extract is currently of great interest to researchers due to its high concentration of chlorogenic acid (CGA) and its potential health benefits. CGA constitutes 6 to 10% of the dry weight of the extract and, due to its anti-inflammatory properties, is a promising natural supplement and agent with therapeutic applications. The purpose of our study was to discover the effects of CGA on peripheral blood mononuclear cell proliferation, and the production of pro- and anti-inflammatory cytokines as well as reactive oxidative species (ROS) in horses during exercise. According to the findings, CGA can affect the proliferation of T helper cells. In addition, at a dose of 50 g/mL, CGA increased the activation of CD4+FoxP3+ and CD8+FoxP3+ regulatory cells. Physical activity decreases ROS production in CD5+ monocytes, but this effect depends on the concentration of CGA, and the effect of exercise on oxidative stress was lower in CD14+ than in CD5+ cells. Regardless of CGA content, CGA significantly increased the release of the anti-inflammatory cytokine IL-10. Moreover, the production of IL-17 was greater in cells treated with 50 g/mL of CGA from beginners compared to the control and advanced groups of horses. Our findings suggest that CGA may have immune-enhancing properties. This opens new avenues of research into the mechanisms of action of CGA and possible applications in prevention and health promotion in sport animals. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the relationship between immunological markers and the dysfunction of cutaneous microcirculation in young patients with type 1 diabetes. The study group consisted of 46 young patients with type 1 diabetes and no associated complications. Microvascular function was assessed with the use of nail fold capillaroscopy before and after implementing post-occlusive reactive hyperemia. This evaluation was then repeated after 12 months. Patients were divided into two subgroups according to their baseline median coverage (defined as the ratio of capillary surface area to surface area of the image area), which was established during the initial exam (coverageBASE). Additionally, the levels of several serum biomarkers, including VEGF, TNF-a and IL-35, were assessed at the time of the initial examination. HbA1c levels obtained at baseline and after a 12-month interval were also obtained. Mean HbA1c levels obtained during the first two years of the course of the disease were also analyzed. Patients with coverageBASE below 16.85% were found to have higher levels of VEGF and TNF-α, as well as higher levels of HbA1c during the first two years following diabetes diagnosis. Our results support the hypothesis that the development of diabetic complications is strongly influenced by metabolic memory and an imbalance of pro- and anti-inflammatory cytokines, regardless of achieving adequate glycemic control. [ABSTRACT FROM AUTHOR]

Leucine-rich repeat kinase 2 (LRRK2) is known to play a crucial role in the pathophysiology of neurodegenerative disorders such as Parkinson’s disease. LRRK2 is predominantly expressed in the lung as well as the brain. However, it is unclear whether LRRK2 expression correlates with the pathogenesis of lung squamous cell carcinoma (LUSC). This study analyzes the prognostic significance of LRRK2 in LUSC using the Kaplan-Meier plotter tool. High expression of LRRK2 is known to be associated with a bad prognosis in patients with LUSC. Patients with high LRRK2 expression, tumor mutational burden, high neoantigen load, and even gender correlation reportedly have the worse survival rates. In the gene expression profiling interactive analysis (GEPIA) database, the severity of pathogenesis in LUSC with high LRRK2 expression positively corresponds to a high expression of anti-inflammatory cytokines but not inflammatory cytokines. Similarly, the increased expression of interleukin (IL)10-related genes was shown to be significantly linked in LRRK2-high LUSC patients having a poor prognosis. Moreover, the tumor immune estimation resource (TIMER) database suggests that macrophages are one of the cellular sources of IL10 in LRRK2-high LUSC patients. Collectively, our results demonstrate that the postulated LRRK2-IL10 axis is a potential therapeutic target and prognostic biomarker for LUSC.

Cutibacterium acnes (C. acnes) is involved in the pathogenesis of acne by inducing inflammation and biofilm formation, along with other virulence factors. A Camellia sinensis (C. sinensis) callus lysate is proposed to reduce these effects. The aim of the present work is to study the anti-inflammatory properties of a callus extract from C. sinensis on C. acnes-stimulated human keratinocytes and the quorum-quenching activities. Keratinocytes were stimulated with thermo-inactivated pathogenic C. acnes and were treated with the herbal lysate (0.25% w/w) to evaluate its anti-inflammatory effect. C. acnes biofilm was developed in vitro and treated with 2.5 and 5% w/w of the lysate to evaluate quorum sensing and the lipase activity. The results showed that the lysate was able to reduce the production of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine ligand 1 (CXCL1), and decrease the nuclear translocation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB). The lysate did not show bactericidal activity but showed diminished biofilm formation, the lipase activity, and the production of autoinducer 2 (AI-2), a member of a family of signaling molecules used in quorum sensing. Therefore, the proposed callus lysate could have the potential to reduce acne-related symptoms without the eradication of C. acnes, which is part of the natural skin microbiome.

Background: Severe malaria (SM) is a fatal multi-system disease which accounted for an estimated 619,000 deaths in 2021. Less than 30% of children presenting with SM are diagnosed and treated promptly, resulting in increased mortality and neurologic impairments in survivors. Studies have identified cytokine profiles that differentiate the various clinical manifestations of malaria (severe and uncomplicated). However, the diagnostic capability of these cytokines in differentiating between the disease states in terms of cut-off values has not yet been determined. Methods: The plasma levels of 22 pro-inflammatory cytokines (Eotaxin/CCL 11, interferon-gamma (IFN-γ), interleukin (IL)- 2, IL-6, IL-1β, IL-12p40/p70, IL-17A, RANTES, MCP-1, IL-15, IL-5, IL-1RA, IL-2R, IFN-α, IP-10, TNF, MIG, MIP-1α, MIP-1β, IL-7, IL-8 and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), and 3 anti-inflammatory cytokines-(IL-4, IL-13 and IL-10) in patients with SM, uncomplicated malaria (UM) and other febrile conditions, were measured and compared using the Human Cytokine Magnetic 25-Plex Panel. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of these cytokines. Results: The level of the pro-inflammatory cytokine, IL-17A, was significantly higher in the SM group as compared to the UM group. Levels of the anti-inflammatory cytokines however did not differ significantly among the SM and UM groups. Only IL-1β and IL-17A showed good diagnostic potential after ROC curve analysis. Conclusion: The data show that levels of pro-inflammatory cytokines correlate with malaria disease severity. IL-1β and IL-17A showed good diagnostic potentials and can be considered for use in clinical practice to target treatment. [ABSTRACT FROM AUTHOR]

Aim: to investigate the effect of teichoic acid Staphylococcus aureus for expression of pro-inflammatory cytokines and of TLR4 in a human small cell lung carcinoma cell line NCI-H69, and cisplatin resistant subline NCI-H69/CPR. Methods. Incubation of cells with teichoic acid (1 ng/m) conducted for 2 days. Expression level of TLR4, TGF-β, INF-γ, TNF-α was evaluated by the real time PCR on 7500 Real-Time PCR System, using specific primers and fluorochrome SYBR Green. The reverse transcription reaction was performed with High-Capacity cDNA Reverse Transcription Kit carried out under the conditions: 25 °C - 10 min, 37 °C ‒ 120 min and 85 °C ‒ 5 min. Results. In cell line culture NCI-H69 addition of teichoic acid increased expression of TLR4 by 1.3 times, and IFN-γ – by 1,1 times. Expression of TGF-β and TNF-α was decreased 2.5 and 4.9 times respectively. In cell line culture NCI-H69/CPR the addition of teichoic acid inhibited the expression of all studied parameters. Expression TLR4 decreased by 4.2 times, IFN-γ – by 1.4 times. Expression TGF-β and TNF-α was depressed 1.6 and 1.2 times. The presented data indicate that teichoic acid of bacterial origin provided the effect of modulating the inflammatory effect in lung cancer cell culture, sensitive and resistant to cisplatin. Conclusions. Teichoic acid as a ligand of TLR4 modulates the expression of pro-inflammatory and anti-inflammatory cytokines in small cell lung cancer cell culture and suppresses the expression of TLR4 and all investigated cytokines in the cisplatin-resistant cell line NCI-H69.

Delayed wound healing in diabetes mellitus (DM) is due to the overlapping phases of the healing process. The prolonged inflammation and altered levels of inflammatory cytokines lead to deformed cell proliferation. Photobiomodulation alleviates the expression of inflammatory cytokines and promotes tissue repair, thereby restoring the wound healing process. To find out the effect of photobiomodulation therapy (PBMT) in the healing dynamics of diabetic wounds with particular emphasis on interleukin-6, interleukin-1β, and tumour necrosis factor-α. Scientific databases searched using keywords of the population: DM, intervention: PBMT, and outcomes: inflammatory cytokines. We have included five preclinical studies in the present systematic review for qualitative analysis. These studies evaluated the effect of PBMT at different wavelengths, dosage, and time on wound healing in DM. The systematic review concludes that PBMT regulates inflammatory cytokines levels, enhances cell proliferation, and migration, thereby improving the wound healing properties. [ABSTRACT FROM AUTHOR]

Copper is a trace element of biological significance that can form complexes with several thiol containing compounds which can be used as filler in biomedical polyurethanes. In this work, segmented polyurethanes (SPUs) were synthesized with thiol containing compounds as chain extenders including d-penicillamine (DP), l-penicillamine (LP), l-cysteine (LC) and reduced glutathione (GR). Then, the synthesized polyurethane was filled with copper chelates based on the same chain extenders. Evidence of free thiol containing chain extender in polyurethane was not observed by FTIR and Raman but EDX provided evidence of sulfur in the unfilled polyurethane and copper and sulfur in their composite. DSC and DRX showed the semi-crystalline nature of the polyurethanes which provided good mechanical properties, especially to those prepared with DP. The Tg of the PCL determined by DMA shifted toward higher temperatures by the addition of copper complexes while TGA studies showed that the thermal degradation was slightly improved when LCCu and GRCu complex were added. Macrophage viability was observed in all composition studied after longer times of extraction (72 h) and dilutions (1:2 to 1:32) but remarkably high in those prepared with LCCu and GRCu. The anti-inflammatory response was proved in LC and GR copper complex filled polyurethanes as IL-4 and IL-10 increased with time while IL-1β and TNF-α were reduced. [ABSTRACT FROM AUTHOR]

In inflammatory bowel disease, dysregulated T cells express pro-inflammatory cytokines. Using a chronic azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis model resembling ulcerative colitis, we evaluated whether and when treatment with the Janus kinase (JAK) inhibitor tofacitinib could be curative. Comparing the treatment with two and three cycles of tofacitinib medication in drinking water – intermittently with DSS induction – revealed that two cycles were not only sufficient but also superior over the 3-x regimen. The two cycles of the 2-x protocol paralleled the second and third cycles of the longer protocol. T cells were less able to express interferon gamma (IFN-γ) and the serum levels of IFN-γ, interleukin (IL)-2, IL-6, IL-17, and tumor necrosis factor (TNF) were significantly reduced in sera, while those of IL-10 and IL-22 increased under the 2-x protocol. Likewise, the frequency and effector phenotype of regulatory T cells (Tregs) increased. This was accompanied by normal weight gain, controlled clinical scores, and restored stool consistency. The general and histologic appearance of the colons revealed healing and tissue intactness. Importantly, two phases of tofacitinib medication completely prevented AOM-incited pseudopolyps and the hyper-proliferation of epithelia, which was in contrast to the 3-x regimen. This implies that the initial IBD-induced cytokine expression is not necessarily harmful as long as inflammatory signaling can later be suppressed and that time-restricted treatment allows for anti-inflammatory and tissue-healing cytokine activities. [ABSTRACT FROM AUTHOR]

Copyright of Revista Cientifica de la Facultade de Veterinaria is the property of Universidad del Zulia, Facultad de Ciencias Veterinarias and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study investigated the hormonal, inflammatory, oxidant–antioxidant, and histopathological effects of exogenous Melatonin administration on Spermatogenesis in rats' chronic unpredictable stress model (CUSM). In the study, stress caused a decrease in follicle stimulating–hormone (FSH), luteinizing hormone (LH), Testosterone, Melatonin, Glutathione (GSH), Glutathione peroxidase (GSH–Px), catalase, interleukin 10 (IL–10) levels and motility, and an increase in Corticosterone, nuclear factor kappa beta (NF–kB), tumor necrosis factor–alpha (TNF–α), interleukin 1 beta (IL–1β), interleukin 6 (IL–6), abnormal sperm, dead/live sperm ratio and exogenous Melatonin reduced inflammatory cytokines and oxidative stress and improved spermatological parameters (P

The immunoprotective functions of microglia in the brain are mediated by the inflammatory M1 phenotype. This phenotype is challenged by anti-inflammatory cytokines which polarize the microglia cells to an immunosuppressive M2 phenotype, a trait that is often exploited by cancer cells to evade immune recognition and promote tumor growth. Investigating the molecular determinants of this behavior is crucial for advancing the understanding of the mechanisms that cancer cells use to escape immune attack. In this article, we describe liquid chromatography (LC)-mass spectrometry (MS)/proteomic data acquired with an EASY-nanoLC 1200-Q ExactiveTM OrbitrapTM mass spectrometer that reflect the response of human microglia cells (HMC3) to stimulation with potential cancer-released anti-inflammatory cytokines known to be key players in promoting tumorigenesis in the brain (IL-4, IL-13, IL-10, TGFB and MCP-1). The MS files were processed with the Proteome Discoverer v.2.4 software package. The cell culture conditions, the sample preparation protocols, the MS acquisition parameters, and the data processing approach are described in detail. The RAW and processed MS files associated with this work were deposited in the PRIDE partner repository of the ProteomeXchange Consortium with the dataset identifiers PXD023163 and PXD023166, and the analyzed data in the Mendeley Data cloud-based repository with DOI 10.17632/fvhw2zwt5d.1. The biological interpretation of the data can be accessed in the research article “Systems-Level Proteomics Evaluation of Microglia Response to Tumor-Supportive Anti-inflammatory Cytokines” (Shreya Ahuja and Iulia M. Lazar, Frontiers in Immunology 2021 [1]). The proteome data described in this article will benefit researchers who are either interested in re-processing the data with alternative search engines and filtering criteria, and/or exploring the data in more depth to advance the understanding of cancer progression and the discovery of novel biomarkers or drug targets.

Endometriosis is a chronic inflammatory disease, which explains the pain that such patients report. Currently, we are faced with ineffective, non-invasive diagnostic methods and treatments that come with multiple side effects and high recurrence rates for both the disease and pain. These are the reasons why we are exploring the possibility of the involvement of pro-inflammatory and anti-inflammatory molecules in the process of the appearance of endometriosis. Cytokines play an important role in the progression of endometriosis, influencing cell proliferation and differentiation. Pro-inflammatory molecules are found in intrafollicular fluid. They have an impact on the number of mature and optimal-quality oocytes. Endometriosis affects fertility, and the involvement of endometriosis in embryo transfer during in vitro fertilization (IVF) is being investigated in several studies. Furthermore, the reciprocal influence between anti-inflammatory and pro-inflammatory cytokines and their role in the pathogenesis of endometriosis has been assessed. Today, we can affirm that pro-inflammatory and anti-inflammatory cytokines play roles in survival, growth, differentiation, invasion, angiogenesis, and immune escape, which provides a perspective for approaching future clinical implications and can be used as biomarkers or therapy.

In inflammatory bowel disease, dysregulated T cells express pro-inflammatory cytokines. Using a chronic azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis model resembling ulcerative colitis, we evaluated whether and when treatment with the Janus kinase (JAK) inhibitor tofacitinib could be curative. Comparing the treatment with two and three cycles of tofacitinib medication in drinking water – intermittently with DSS induction – revealed that two cycles were not only sufficient but also superior over the 3-x regimen. The two cycles of the 2-x protocol paralleled the second and third cycles of the longer protocol. T cells were less able to express interferon gamma (IFN-γ) and the serum levels of IFN-γ, interleukin (IL)-2, IL-6, IL-17, and tumor necrosis factor (TNF) were significantly reduced in sera, while those of IL-10 and IL-22 increased under the 2-x protocol. Likewise, the frequency and effector phenotype of regulatory T cells (Tregs) increased. This was accompanied by normal weight gain, controlled clinical scores, and restored stool consistency. The general and histologic appearance of the colons revealed healing and tissue intactness. Importantly, two phases of tofacitinib medication completely prevented AOM-incited pseudopolyps and the hyper-proliferation of epithelia, which was in contrast to the 3-x regimen. This implies that the initial IBD-induced cytokine expression is not necessarily harmful as long as inflammatory signaling can later be suppressed and that time-restricted treatment allows for anti-inflammatory and tissue-healing cytokine activities.

This study tested the prospective associations and potential mediators between subjective aging, indexed by subjective age and self‐perceptions of aging (SPA), and a range of inflammatory markers, including C‐reactive proteins (CRP) and pro‐ and anti‐inflammatory cytokines among older adults. Participants (N = 6099, 59% women, age range = 50 to 94, Mean Age = 65.32, SD = 8.85) were drawn from the Health and Retirement Study. Subjective age, SPA, and demographic factors were assessed in 2008/2010. Assessments of soluble transformation growth factor‐beta 1 (sTGF‐β1), interleukin 10 (IL‐10), interleukin‐1 receptor antagonist (IL‐1Ra), interleukin 6 (IL‐6), soluble tumor necrosis factor receptors (sTNFR1), and high sensitivity CRP (hsCRP) were measured in 2016. Potential mediators (body mass index, disease burden, physical inactivity, and depressive symptoms) were asssessed at baseline and in 2012/2014. Linear regression analyses indicated that an older subjective age and negative SPA were related to higher level of IL‐10, IL‐1Ra, IL‐6, sTNFR1 and hsCRP. These associations were mediated by higher disease burden and physical inactivity. Negative SPA (but not subjective age) was associated with lower sTGF‐β1. The link between subjective aging and inflammatory markers was relatively independent from chronological age. The present study provides new evidence that subjective aging is prospectively associated with inflammation, including systemic inflammation and pro‐and anti‐inflammatory cytokines. Based upon a large sample of older adults, the present study found that an older subjective age and negative self‐perceptions of aging were associated with higher systemic inflammation and pro‐and anti inflammatory cytokines assessed 6 to 8 years later. Furthermore, these associations were partly mediated by disease burden and physical inactivity. This study contributes to knowledge on the psychological correlates of inflammation and more broadly on the psychological factors associated with immunity among older adults. [ABSTRACT FROM AUTHOR]

Inflammation has been shown to be an important feature of atherosclerosis. We aimed to assess a profile of inflammatory cytokines and growth factors in patients with established coronary artery disease (CAD), 12 months after stent implantation. A total of 193 patients with CAD, who were candidates for angiography, 12 months after stent implantation (cases), were compared with 107 patients with CAD, who were candidates for their first angiography (controls). Fasting blood glucose (FBG), triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and high-sensitive C-reactive protein (hs-CRP) were measured using routine methods. The serum concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, MCP-1, EGF and VEGF were determined using competitive chemiluminescence immunoassays. Serum levels of FBG (p =.002), TG (p =.029) and hs-CRP (p =.005) were significantly lower in cases than controls. The cytokines and growth factor profiles in cases were significantly different from controls. After multivariate analysis, serum levels of IL-2 (p <.001), IL-4 (p =.028) were significantly lower in cases compared with the controls while serum levels of IL-8, TNF-α, MCP-1, EGF and VEGF were significantly higher in the cases (p <.001). In patients with CAD and higher consumption of drug used (statins, aspirin and glucose lowering agents) to mitigate the risk of a secondary event, the level of hs-CRP one year after stent implantation decreased despite of significant higher serum levels of pro- and anti-inflammatory cytokines and growth factors. [ABSTRACT FROM AUTHOR]

Introduction: The therapeutic benefits of the brown algae fucoidan in the treatment of breast cancer have attracted considerable interest in recent years. However, research using spheroids which provide relevant results in trials for antitumor and immunomodulatory products because they adequately simulate the tumor microenvironment, is limited. Objective: To evaluate the antitumor and immunomodulatory activity of Lessonia trabeculata fucoidan (LtF), native to the Peruvian Sea, on two types of multicellular tumor spheroids. Methods: The study was conducted from January to December 2021. Two types of spheroides were elaborated: from 4T1 tumor cells (MTS), and from 4T1 tumor cells+mouse splenocytes (MTSs). The antitumor activity of LtF was evaluated in MTS by quantifying cell viability with MTT. Immunomodulatory activity was determined in MTSs using the IC50 for two types of treatment: simple, fucoidan alone (LtF) and combined, fucoidan+doxorubicin (LtF+Dox). Pro-inflammatory (TNF-a, IL-6) and anti-inflammatory (IL-10, TGF-ß) cytokine production was quantified by sandwich ELISA 72 h after treatment. Dox was used as positive control in all assays. Results: LtF exerted antitumor activity as evidenced by increased necrotic zone and cell debris formation compared to the untreated control. Antitumor activity was concentration dependent between 100 and 6 000 µg/ml. In MTSs, simple treatment increased IL-6 and decreased IL-10 and TGF-ß production. The combined treatment significantly reduced TGF-ß production. In both treatments and Dox, there was an increase in IL-6 compared to the untreated control. The highest production of IL-10 and TGF-ß was observed in the untreated control, compatible with a highly immunosuppressive tumor microenvironment. Conclusions: LtF is a good candidate for the treatment of breast cancer and can immunomodulate the tumor microenvironment alone or in combination with Dox. [ABSTRACT FROM AUTHOR]

To determine the mechanisms by which Weizmannia coagulans SANK70258 (WC) supplementation improved growth performance and coccidial symptoms, we assessed the gene expressions and the microbiota compositions in the small intestinal tissues and digestas of coccidium-infected broilers previously given WC or lasalocid-A sodium (AM). WC supplementation significantly upregulated the gene expressions related to intestinal immunity and barrier functions, such as IL17A, IL17F, IL10, cathelicidin-2 and pIgR. Body weights, and Claudin-1 and IL10 expressions were positively correlated (r = 0.41, p < 0.05 and r = 0.37, p = 0.06, respectively), whereas lesion scores of the small intestine and IL17A expression were negatively correlated (r = −0.33, p = 0.09). The microbiota analysis detected that genus Alistipes was more abundant in WC-supplemented broilers than in control, and positively correlated with body weights and Claudin-1 expression (r = 0.61, p < 0.05 and r = 0.51, p < 0.05, respectively). Intriguingly, genus Enterococcus was most abundant in WC-supplemented broilers and positively correlated with IL17A expression (r = 0.49, p < 0.05). Interestingly, Escherichia-Shigella was significantly more abundant in the small intestinal digestas of AM-administered broilers than in those of control. To summarize, WC supplementation modulated and immunostimulated the microbiotas of broilers, specifically genera Alistipes and Enterococcus, which led to the improvement of weight gain and coccidial symptoms, without disrupting the intestinal microbiota compositions, as AM did. [ABSTRACT FROM AUTHOR]

Aim: The major target of this research is to examine whether there is any connection between the levels of vitamin D and anti-inflammatory mediators in patients with fibromyalgia syndrome (FMS). Materials and Methods: The study contains 30 FMS diagnosed and 25 healthy female individuals and the determination of FMS was made according to the standards of 2010 American College of Rheumatology (ACR). Vitamin D, vitamin D receptor (VDR), vitamin D binding protein (VDBP) levels, and anti-inflammatory cytokine (IL-4, IL-10, TGF-β) levels in the serum of patients with FMS and healthy individuals were measured using enzyme-linked immunosorbent assay (ELISA). Results: The concentrations of vitamin D, VDR, and VDBP were determined to be higher in healthy controls than in patients with FMS (p<0.001). Correlating with this, IL-4, IL-10, and TGF-β levels were measured remarkably higher in the healthy group than in the FMS patients (p<0.001). Conclusion: Low vitamin D levels may cause a decrease in anti-inflammatory cytokine levels and their immunosuppressive effect in FMS. [ABSTRACT FROM AUTHOR]

Objective: identify the nature of anti-inflammatory and pro-inflammatory cytokine regulation in different periods of plasma cell myeloma (PCM) natural history with evaluation of its role as a prognostic criterion for the disease course in the Chornobyl NPP (ChNPP) accident survivors. Materials and methods. Levels of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines both with their relationship were studied in the stage I-II and stage III PCM patients (n = 74) in different periods of the disease natural history i.e. remission/stabilization and progression. Study groups included the ChNPP accident survivors (n = 35) and non-irradiated subjects (n = 39). Immunoenzymatic method was applied using the Vector-Best CJSC commercial kits. Results. There was a unidirectional increase in the levels of IL-6, TNF-α, and IL-10 in irradiated persons, and an elevation of IL-6 and TNF-α; concentration but with a decreased level of IL-10 in non-irradiated subjects compared to control at the time of PCM diagnosis. Period of the disease remission/stabilization in PCM stage I-II patients featured a decrease in IL-6 concentration regardless of the exposure to ionizing radiation, while TNF-α content remained at the level of the control group. There was a significant increase in IL-6 concentration in both study groups during the disease relapse, while TNF-α level remained unchanged compared to stabilization phase of the disease. According to the obtained data a certain contribution of radiation exposure to the PCM pathogenesis as a possible predictor of the exacerbated disease course cannon be excluded. Conclusion. Determining the serum level of pro-inflammatory and anti-inflammatory cytokines (IL-6, TNF-α and IL-10 respectively) provides advancement in assessment of the PCM course and predict the effectiveness of administration of therapy protocols. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a common disorder caused by immune system dysregulation. The present contribution describes a randomized, double-blind, placebo-controlled comparative evaluation of the influence of a unique food-grade co-delivery form of curcumin and ashwagandha extracts (CQAB) in comparison to a bioavailable curcumin formulation (CGM) and placebo employing healthy participants, (n = 96), characterized with mild AR. The subjective measurements (TNSS, BIS and POMS-SF questionnaires) clearly demonstrated the efficacy of CQAB over CGM in the alleviation of AR symptoms and hence the quality of life. Further, CQAB administration also showed significant modulation of biochemical parameters (significant decrease in Th2 cytokines, pro-inflammatory cytokines, CD4+/CD8+ ratio and IgE, and a significant increase in Th1 cytokines, anti-inflammatory cytokine IL-10 as well as for the immunoglobulins IgG, IgM, and IgA) in support of its improved immune-balancing effect, compared to CGM. Both CQAB and CGM were well tolerated without any adverse events. [Display omitted] • Hydrogel-based co-delivery of curcumin and ashwagandha extracts (CQAB). • CQAB alleviated allergic rhinitis symptoms safely. • CQAB helped to improve sleep and reduce fatigue. • CQAB demonstrated Th1/Th2 balance, modulated cytokines and CD4+/CD8+ ratio. • Randomized, double-blind, placebo-controlled clinical trial. [ABSTRACT FROM AUTHOR]

Menopause is an age-related change that persists for around one-third of a woman's life. Menopause increases the risk of metabolic illnesses such as diabetes, osteoporosis (OP), and nonalcoholic fatty liver disease (NAFLD). Immune mediators (pro-inflammatory cytokines), such as interleukin-1 (IL-1), IL-6, IL-17, transforming growth factor (TGF), and tumor necrosis factor (TNF), exacerbate the challenges of a woman undergoing menopause by causing inflammation and contributing to the development of these metabolic diseases in postmenopausal women. Furthermore, studies have shown that anti-inflammatory cytokines such as interleukin-1 receptor antagonists (IL-1Ra), IL-2, and IL-10 have a double-edged effect on diabetes and OP. Likewise, several interferon (IFN) members are double-edged swords in the OP. Therefore, addressing these immune mediators precisely may be an approach to improving the health of postmenopausal women. Hence, considering the significant changes in these cytokines, the present review focuses on the latest findings concerning the molecular mechanisms by which pro- and anti-inflammatory cytokines (interleukins) impact postmenopausal women with diabetes, OP, and NAFLD. Furthermore, we comprehensively discuss the therapeutic approaches that identify cytokines as therapeutic targets, such as hormonal therapy, physical activities, natural inhibitors (drugs), and others. Finally, this review aims to provide valuable insights into the role of cytokines in postmenopausal women's diabetes, OP, and NAFLD. Deeply investigating the mechanisms and therapeutic interventions involved will address the characteristics of immune mediators (cytokines) and improve the management of these illnesses, thereby enhancing the general quality of life and health of the corresponding populations of women. [Display omitted] • Pro-inflammatory cytokines worsen menopause complications and contribute to metabolic diseases like diabetes, osteoporosis, and NAFLD. • Anti-inflammatory cytokines have a double-edged effect on both diabetes and osteoporosis. • Pro- and anti-inflammatory cytokines in metabolic illnesses may support diagnosis and treatment strategies for menopausal patients. • Inhibitors of pro-inflammatory cytokines can enhance the prevention and diagnosis of metabolic illnesses. [ABSTRACT FROM AUTHOR]