Anti-inflammatory Cytokine Profile Research Articles

Cardiac fibroblast cytokine profiles induced by proinflammatory or profibrotic stimuli promote monocyte recruitment and modulate macrophage M1/M2 balance in vitro

Macrophage polarization plays an essential role in cardiac remodeling after injury, evolving from an initial accumulation of proinflammatory M1 macrophages to a greater balance of anti-inflammatory M2 macrophages. Whether cardiac fibroblasts themselves influence this process remains an intriguing question. In this work, we present evidence for a role of cardiac fibroblasts (CF) as regulators of macrophage recruitment and skewing. Adult rat CF, were treated with lipopolysaccharide (LPS) or TGF-β1, to evaluate ICAM-1 and VCAM-1 expression using Western blot and proinflammatory/profibrotic cytokine secretion using LUMINEX. We performed in vitro migration and adhesion assays of rat spleen monocytes to layers of TGF-β1- or LPS-pretreated CF. Finally, TGF-β1- or LPS-pretreated CF were co-cultured with monocyte, to evaluate their effects on macrophage polarization, using flow cytometry and cytokine secretion.There was a significant increase in monocyte adhesion to LPS- or TGF-β1-stimulated CF, associated with increased CF expression of ICAM-1 and VCAM-1. siRNA silencing of either ICAM-1 or VCAM-1 inhibited monocyte adhesion to LPS-pretreated CF; however, monocyte adhesion to TGF-β1-treated CF was dependent on only VCAM-1 expression. Pretreatment of CF with LPS or TGF-β1 increased monocyte migration to CF, and this effect was completely abolished with an MCP-1 antibody blockade. LPS-treated CF secreted elevated levels of TNF-α and MCP-1, and when co-cultured with monocyte, LPS-treated CF stimulated increased macrophage M1 polarization and secretion of proinflammatory cytokines (TNF-α, IL-12 and MCP-1). On the other hand, CF stimulated with TGF-β1 produced an anti-inflammatory cytokine profile (high IL-10 and IL-5, low TNF-α). When co-cultured with monocytes, the TGF-β1 stimulated fibroblasts skewed monocyte differentiation towards M2 macrophages accompanied by increased IL-10 and decreased IL-12 levels. Taken together, our results show for the first time that CF can recruit monocytes (via MCP-1-mediated chemotaxis and adhesion to ICAM-1/VCAM-1) and induce their differentiation to M1 or M2 macrophages (through the CF cytokine profile induced by proinflammatory or profibrotic stimuli).

Pro- and anti-inflammatory cytokine profiles in cerebrospinal fluid before first and then two consecutive WJ-MSC transplantations in ALS patients

Pro- and anti-inflammatory cytokine profiles in cerebrospinal fluid before first and then two consecutive WJ-MSC transplantations in ALS patients

Circadian rhythm abnormalities - Association with the course of inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are the main representatives of inflammatory bowel diseases (IBD), a group of chronic, immune system-mediated inflammatory diseases of the gastrointestinal (GI) tract. The pathogenesis of the intestinal lesions in IBD is not entirely identified and understood: excessive activation of the immune system may come as a result of the interaction of various environmental and infectious factors, genetic predisposition, and the mediation of abnormal intestinal flora. The main objective of the current study is to further identify the risk factors for the development of IBD. Currently, there is very little knowledge about circadian rhythm and IBD and there are only a few studies on the relationship between sleep disturbances and the course of the disease, as well as pro- and anti-inflammatory cytokine profile and general immune system functioning. Furthermore, the relationship between the expression of circadian rhythm genes and severe course of IBD is still unknown. The aim of this review is to show the current state of knowledge about the relationship between circadian rhythm disorders, sleep disturbance and inflammation in the GI tract and to analyze the possibility of employing this knowledge in diagnosis and treatment of IBD.

Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes.

Factor H (FH) binds apoptotic cells to limit the inflammatory potential of complement. Here we report that FH is actively internalized by apoptotic cells to enhance cathepsin L-mediated cleavage of endogenously expressed C3, which results in increased surface opsonization with iC3b. In addition, internalized FH forms complexes with nucleosomes, facilitates their phagocytosis by monocytes and induces an anti-inflammatory biased cytokine profile. A similar cytokine response was noted for apoptotic cells coated with FH, confirming that FH diminishes the immunogenic and inflammatory potential of autoantigens. These findings were supported by in vivo observations from CFH(-/-) MRL-lpr mice, which exhibited higher levels of circulating nucleosomes and necrotic cells than their CFH(+/+) littermates. This unconventional function of FH broadens the established view of apoptotic cell clearance and appears particularly important considering the strong associations with genetic FH alterations and diseases such as systemic lupus erythematosus and age-related macular degeneration.

Immunomodulatory Effects of 1,25-Dihydroxyvitamin D3 on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens.

While emerging evidence indicates that dendritic cells (DC) play a central role in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory agents provides prospect as disease-modifying therapy. Our observations reveal that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment of monocyte-derived DC results in a semimature phenotype and anti-inflammatory cytokine profile as compared to conventional DC, in both healthy controls and MS patients. Importantly, 1,25(OH)2D3-treated DC induce T cell hyporesponsiveness, as demonstrated in an allogeneic mixed leukocyte reaction. Next, following a freeze-thaw cycle, 1,25(OH)2D3-treated immature DC could be recovered with a 78% yield and 75% viability. Cryopreservation did not affect the expression of membrane markers by 1,25(OH)2D3-treated DC nor their capacity to induce T cell hyporesponsiveness. In addition, the T cell hyporesponsiveness induced by 1,25(OH)2D3-treated DC is antigen-specific and robust since T cells retain their capacity to respond to an unrelated antigen and do not reactivate upon rechallenge with fully mature conventional DC, respectively. These observations underline the clinical potential of tolerogenic DC (tolDC) to correct the immunological imbalance in MS. Furthermore, the feasibility to cryopreserve highly potent tolDC will, ultimately, contribute to the large-scale production and the widely applicable use of tolDC.

IMMUNOLOGICAL EVALUATION OF PATIENTS WITH TYPE 2 DIABETES MELLITUS SUBMITTED TO METABOLIC SURGERY.

Background : Immunological and inflammatory mechanisms play a key role in the development and progression of type 2 diabetes mellitus. Aim : To raise the hypothesis that alterations in immunological parameters occur after duodenojejunal bypass surgery combined with ileal interposition without gastrectomy, and influences the insulin metabolism of betacells.Methods : Seventeen patients with type 2 diabetes mellitus under clinical management were submitted to surgery and blood samples were collected before and six months after surgery for evaluation of the serum profile of proinflammatory (IFN-γ, TNF-α, IL-17A) and anti-inflammatory cytokines (IL-4, IL-10). In addition, anthropometric measures, glucose levels and insulin use were evaluated in each patient. Results : No changes in the expression pattern of proinflammatory cytokines were observed before and after surgery. In contrast, there was a significant decrease in IL-10 expression, which coincided with a reduction in the daily insulin dose, glycemic index, and BMI of the patients. Early presentation of food to the ileum may have induced the production of incretins such as GLP-1 and PYY which, together with glycemic control, contributed to weight loss, diabetes remission and the consequent good surgical prognosis of these patients. In addition, the control of metabolic syndrome was responsible for the reduction of IL-10 expression in these patients. Conclusion : These findings suggest the presence of low-grade inflammation in these patients during the postoperative period, certainly as a result of adequate glycemic control and absence of obesity, contributing to a good outcome of surgery.

The pro-inflammatory and anti-inflammatory cytokine profile in peripheral blood of women with recurrent implantation failure

Limited information is available on the balance state of pro- and anti-inflammatory cytokines in patients with recurrent implantation failure (RIF). This study assessed the pro- and anti-inflammatory cytokines in plasma of 34 patients with RIF, compared with those of 25 women with a successful pregnancy in the first IVF/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI–ET) cycle. The IFN-γ, IL-1β, IL-6 and IL-4 concentrations were higher, whereas the TGF-β1 concentration was lower in the RIF group compared with the control group. Furthermore, the ratios of pro-inflammatory and anti-inflammatory cytokines IFN-γ/IL-4, IFN-γ/IL-10, IFN-γ/TGF-β1, IL-6/IL-10, IL-6/TGF-β1, IL-1β/TGF-β1 and TNF-α/TGF-β1 were higher in the RIF group (all P < 0.01). The results suggested a shift toward a pro-inflammatory state in peripheral blood of the patients with RIF.

TIGIT negatively regulates inflammation by altering macrophage phenotype

Macrophages function as an essential component of innate immune system, contributing to both the initiation and appropriate resolution of inflammation. The exposure of macrophages to the microbial products, such as lipopolysaccharide (LPS), can strongly shift the balance between tissue homeostasis and inflammation in favor of causing systemic damage, in which macrophage M1 polarization play important roles. Strategies aiming at restoring the balance of macrophage polarization remain to be further explored. Herein, we have demonstrated that poliovirus receptor(PVR), the receptor of TIGIT, was dramatically upregulated on the surface of mouse peritoneal macrophages when exposed to LPS. TIGIT-Fc fusion protein not only inhibited the macrophage activation, but also skewed M1/M2 balance toward an anti-inflammatory profile, especially enhanced the secretion of IL-10. The activation of TIGIT/PVR pathway in macrophages correlated with increased nuclear translocation of c-Maf, which promotes IL-10 transcription. Treatment with fibroblasts stably secreting TIGIT-Fc fusion protein significantly reversed the lethal and sublethal endotoxic shock, which facilitated peritoneal macrophages to switch towards anti-inflammatory M2 cytokine profiles. These findings highlight a novel role of the TIGIT/PVR pathway in macrophage M2 polarization and suggest that TIGIT may have the potential to optimize the treatment of macrophage-involved inflammatory diseases.

Abstract 19: Deletion of Myeloid GSK3α Attenuates Atherosclerosis and Promotes an M2 Macrophage Phenotype

Objective: Glycogen synthase kinase (GSK)-3α/β has been implicated in the pathogenesis of diseases including diabetes, cancer, Alzheimer’s and atherosclerosis. The tissue and homolog specific functions of GSK3α and β in atherosclerosis are unknown. This study examines the effect of hepatocyte or myeloid cell specific deletion of GSK3α or GSK3β on atherosclerosis in LDLR-/- mice. Approach and results: We ablated GSK3α or GSK3β expression in hepatic or myeloid cells of LDLR-/- mice and mice were fed a high fat diet for 10 weeks. GSK3α or GSK3β deficiency in hepatic or myeloid cells did not affect metabolic parameters, including plasma lipid levels. Hepatic deletion of GSK3α or GSK3β did not affect the development of atherosclerosis or hepatic lipid content. Myeloid deletion of GSK3α, but not GSK3β, reduced atherosclerotic lesion volume as well as lesion complexity. Mice lacking GSK3α in myeloid cells had a less inflammatory and more anti-inflammatory plasma cytokine profile. Macrophages within atherosclerotic lesions of myeloid GSK3α deficient mice, but not GSK3β deficient mice, displayed reduced expression of markers associated with M1 macrophage polarization and enhanced expression of the M2 markers. Finally, bone marrow derived macrophages were isolated and differentiated into classical M1 macrophages or alternative M2 macrophages in vitro. GSK3α deletion, but not GSK3β deletion, attenuated the expression of genes associated with M1 polarization while promoting the expression of genes associated with M2 polarization. Mechanistically, GSK3α regulated macrophage polarization by modulating the phosphorylation and activation of STAT transcription factors. Conclusions: Our findings suggest that deletion of myeloid GSK3α attenuates the progression of atherosclerosis by regulating STAT activation and promoting an M2 macrophage phenotype.

Impact of Gut Microbiome Modulation on Gut Inflammation

Direct fed microbial products have been the focus of considerable scientific and public interest as we learn how the gut microbiome impacts host health and immune function. Previous research in our lab has demonstrated supplementation with a lactic acid bacteria (LAB) product results in an anti‐inflammatory host phenotype. It is also associated with an anti‐inflammatory cytokine profile in the ileum (↑ IL‐10, ↓ IL‐12RB2). However, the mechanisms behind this effect remain unknown. We hypothesized that the LAB product would stimulate the presence of bacteria with an anti‐inflammatory effect on the gut mucosa and/or suppress inflammatory species. Following supplementation with 3x105 CFU LAB (Lactobacillus acidophilus, Lactobacillus casei, Enterococcus faecium, and Bifidobacterium bifidium)/g feed from day of hatch, we evaluated the gut microbiome of 28‐day old chickens at 5 gastrointestinal locations. Microbial DNA was isolated from 5 samples/treatment x location and sequenced using Illumina MiSeq paired end sequencing. The sequence reads were processed and analyzed with Qiime and Primer‐E. Analysis of intestinal samples revealed upward shifts in Lactobacillus following supplementation, as well as a sharp decline in segmented filamentous bacteria (SFB) in the ileum. Though they have been observed in the ileum of many species for decades, the taxonomic identification of these bacteria is relatively recent, as is understanding of their role in stimulating gut inflammation through TH17 cells. These data suggest this LAB consortium works to decrease levels of SFM in the ileum, which may result in less ileal inflammation. This could reduce gut inflammation, reducing irritation and improving digestive efficiency.

Deletion of Myeloid GSK3α Attenuates Atherosclerosis and Promotes an M2 Macrophage Phenotype.

Glycogen synthase kinase (GSK)-3α/β has been implicated in the pathogenesis of diabetes mellitus, cancer, Alzheimer, and atherosclerosis. The tissue- and homolog-specific functions of GSK3α and β in atherosclerosis are unknown. This study examines the effect of hepatocyte or myeloid cell deletion of GSK3α or GSK3β on atherosclerosis in low-density lipoprotein receptor (LDLR)(-/-) mice. We ablated GSK3α or GSK3β expression in hepatic or myeloid cells of LDLR(-/-) mice, and mice were fed a high-fat diet for 10 weeks. GSK3α or GSK3β deficiency in hepatic or myeloid cells did not affect metabolic parameters, including plasma lipid levels. Hepatic deletion of GSK3α or GSK3β did not affect the development of atherosclerosis or hepatic lipid content. Myeloid deletion of GSK3α, but not of GSK3β, reduced atherosclerotic lesion volume and lesion complexity. Mice lacking GSK3α in myeloid cells had a less inflammatory and more anti-inflammatory plasma cytokine profile. Macrophages within atherosclerotic lesions of myeloid GSK3α-deficient mice, but not of GSK3β-deficient mice, displayed reduced expression of markers associated with M1 macrophage polarization and enhanced expression of the M2 markers. Finally, bone marrow-derived macrophages were isolated and differentiated into classical M1 macrophages or alternative M2 macrophages in vitro. GSK3α deletion, but not GSK3β deletion, attenuated the expression of genes associated with M1 polarization while promoting the expression of genes associated with M2 polarization by modulating STAT3 and STAT6 activation. Our findings suggest that deletion of myeloid GSK3α attenuates the progression of atherosclerosis by promoting an M2 macrophage phenotype.

Bifidobacterium pseudocatenulatum CECT7765 promotes a TLR2-dependent anti-inflammatory response in intestinal lymphocytes from mice with cirrhosis.

Intestinal homeostasis plays an important role in bacteria-derived complications in cirrhosis. Intestinal lymphocytes are responsible for immune effector functions and can be modulated by certain probiotics. We evaluate the interaction between Bifidobacterium pseudocatenulatum CECT7765 and intestinal lymphocytes in mice with cirrhosis. Cirrhosis was induced by intragastrical administration of carbon tetrachloride in Balb/C mice. One week prior to laparotomy, animals received B. pseudocatenulatum CECT7765 (10(7), 10(9) or 10(10)cfu/daily) or placebo. Chemokine receptor and cytokine expression were evaluated in intestinal lymphocytes. Gut permeability was studied by FITC-LPS recovery in vivo. Luminal antigens, inflammation and functional markers were evaluated in liver samples. Bifidobacterium pseudocatenulatum CECT7765 decreased the expression of pro-inflammatory chemokine receptors CCR6, CCR9, CXCR3 and CXCR6 in intestinal lymphocytes from cirrhotic mice in a concentration-dependent manner. The bifidobacterial strain induced a shift towards an anti-inflammatory cytokine profile in this cell subset. B. pseudocatenulatum CECT7765-induced inflammatory modulation was TLR2-mediated, as in vitro TLR2 blockade inhibited the reduction of TNF-alpha and its receptors and the increase of IL-10 and IL-10 receptor secretion. The recovery rate of administered fluorescence-labelled endotoxin was significantly and dose-dependently lowered with the bifidobacterial strain. The reduced intestinal permeability was associated with a decreased burden of bacterial antigens in the liver of mice treated with B. pseudocatenulatum CECT7765. Liver function and inflammation were improved with the use of the bifidobacterial strain at the highest dose tested (10(10)cfu). Bifidobacterium pseudocatenulatum CECT7765 improves gut homeostasis and prevents gut-derived complications in experimental chronic liver disease.

Vaccination with Leishmania infantum acidic ribosomal P0 but not with nucleosomal histones proteins controls Leishmania infantum infection in hamsters.

BackgroundSeveral intracellular Leishmania antigens have been identified in order to find a potential vaccine capable of conferring long lasting protection against Leishmania infection. Histones and Acid Ribosomal proteins are already known to induce an effective immune response and have successfully been tested in the cutaneous leishmaniasis mouse model. Here, we investigate the protective ability of L. infantum nucleosomal histones (HIS) and ribosomal acidic protein P0 (LiP0) against L. infantum infection in the hamster model of visceral leishmaniasis using two different strategies: homologous (plasmid DNA only) or heterologous immunization (plasmid DNA plus recombinant protein and adjuvant).Methodology/Principal FindingsImmunization with both antigens using the heterologous strategy presented a high antibody production level while the homologous strategy immunized group showed predominantly a cellular immune response with parasite load reduction. The pcDNA-LiP0 immunized group showed increased expression ratio of IFN-γ/IL-10 and IFN-γ/TGF-β in the lymph nodes before challenge. Two months after infection hamsters immunized with the empty plasmid presented a pro-inflammatory immune response in the early stages of infection with increased expression ratio of IFN-γ/IL-10 and IFN-γ/TGF-β, whereas hamsters immunized with pcDNA-HIS presented an increase only in the ratio IFN-γ/ TGF-β. On the other hand, hamsters immunized with LiP0 did not present any increase in the IFN-γ/TGF-β and IFN-γ/IL-10 ratio independently of the immunization strategy used. Conversely, five months after infection, hamsters immunized with HIS maintained a pro-inflammatory immune response (ratio IFN-γ/ IL-10) while pcDNA-LiP0 immunized hamsters continued showing a balanced cytokine profile of pro and anti-inflammatory cytokines. Moreover we observed a significant reduction in parasite load in the spleen, liver and lymph node in this group compared with controls.Conclusions/SignificanceOur results suggest that vaccination with L. infantum LiP0 antigen administered in a DNA formulation could be considered a potential component in a vaccine formulation against visceral leishmaniasis.

Correlations between Anti-inflammatory Cytokines and Lumbar T Score of Patients with Psoriatic and Rheumatoid Arthritis

Aim: Our aim is to assess comparative interleukin 4 and interleukin 13 levels in serum and in synovial fluid for patients with psoriatic and rheumatoid arthritis as well as comparative evaluation of serum levels of these antiinflammatory cytokines with lumbar T score. Methods: The study was performed on three groups: group 1 consists of 27 patients with psoriatic arthritis, group 2 consists of 21 patients with rheumatoid arthritis, and the control group consists of 20 healthy patients. For each of these groups we have identified the anti-inflammatory cytokines in blood and synovial fluid. We also established a clinically useful correlation between blood concentration of these cytokines and lumbar T score. Results: In group 1 serum IL-4 in most patients showed no detectable serum concentration, and IL- 13 had values between 2.67 and 4.99 pg/ml, p1<0.01-ES, and the lumbar T score was ranged between 1.58 and 1.77 DS, p?1<0.01. In group 2 serum IL-4 in most patients showed no detectable serum concentration, and IL-13 had values between 2.21 and 13.32 pg/ml, p2<0.002-ES, and the lumbar T score had values between -2.51 and -3.41 DS, p?2<0001-ES. In the control group IL-4 was not detected in serum, serum IL- 13 had values between 2.05 and 3.35 pg/ml, and the lumbar T score had values between 0.29 and 1.3 DS. In the synovial fluid the interleukin-4 and interleukin-13 were found in both groups of the patients studied. We also found that in patients with psoriatic arthritis there is an increase in the ratio of the concentration of IL-13 in synovial fluid and blood as opposed to those with rheumatoid arthritis. Conclusion: There are significant differences regarding the profile of anti-inflammatory cytokines from serum and synovial fluid of patients with psoriatic and rheumatoid arthritis, also in psoriatic arthritis exist a local production of interleukin-13 in the inflamed joint.

Proinflammatory and anti-inflammatory cytokine profile in pediatric patients with irritable bowel syndrome

Background and objectivesThere is evidence that patients with irritable bowel syndrome (IBS) have a low degree of inflammation in the intestinal mucosa. The aim of the study was to evaluate theprofile of pro- and anti-inflammatory cytokinesin plasmain Mexican pediatric patients with IBS. Patients and methodsFifteen patients with IBS according to Rome III criteria for childhood and 15 healthy children, matched by age and sex, were included in the study. Plasma levels of tumoral necrosis factor alpha (TNF-α), interleukins 10 and 12 (IL-10, IL-12) and transforming growth factor beta (TGF-β) were quantified and compared between groups. ResultsPlasma levels of IL-10 were lower in patients with IBS (86.07+21.3 pg/mL vs. 118.71+58.62 pg/mL: P=.045) and IL-12 levels were higher in patients with IBS compared to the control group of healthy children (1,204.2±585.9 pg/mL vs. 655.04±557.80 pg/mL; P=.011). The IL-10/IL-12 index was lower in patients with IBS (0.097±0.07 vs. 0.295±0.336; P=.025). Plasma concentration of TGF-β was higher in patients with IBS (545.67±337.69 pg/mL vs. 208.48±142.21 pg/mL; P=.001). There was no difference in plasma levels of TNF-α between groups. ConclusionsThis study suggests that children with IBS have a state of altered immune regulation. This is consistent with the theory of low-grade inflammatory state in these patients. Further studies are needed to elucidate the role played by these cytokines, specifically TGF-β in the pathogenesis of IBS.

Evaluation of mRNA expression of the transcription factors of Th1 and Th2 subsets (T-bet and GATA-3) in periodontal health and disease - A pilot study in south Indian population.

Background:Based on their respective pro- or anti-inflammatory cytokine profiles, the Th1/Th2 paradigm explains pathogenic mechanisms involved in periodontal disease. Establishment of Th1 and Th2 subsets from a naive T-cell precursor depends on transcriptional regulation. The aim of this study was to compare the expression of master transcription factor regulators T-bet and GATA-3, respectively, to indicate the predominance of Th1 and Th2 subsets in the presence and absence of periodontal disease.Materials and Methods:A gingival tissue biopsy sample was obtained from each of 10 severe periodontitis patients (>5 mm attachment loss) and 10 periodontally healthy patients (no attachment loss). Biopsies were immediately processed by real-time reverse transcriptase polymerase chain reaction and the difference in mRNA expression of T-bet and GATA-3 was assessed for each group.Results:The mRNA expression of T-bet was marginally increased about 1.31-fold in disease, while the GATA-3 levels showed a significant decrease of 4.39-fold in disease.Conclusion:The advanced periodontal lesions lack Th2 cells, which produce anti-inflammatory cytokines. The biopsies were therefore dominated by Th1 cells, which activate macrophages and osteoclasts.

Immunomodulatory role of outer membrane vesicles of Shigella in mouse model

In our previous studies, we discussed the protective efficacy of the two types of vaccine formulation namely SOMVs (single-serotype outer membrane vesicles) and MOMVs (multi-serotype outer membrane vesicles). Here, we compared the immunogenic roles of these two types of formulations and also studied general immunomodulation by Shigella OMVs in adult BALB/c mice. The production of various pro-inflammatory (TNF-α, IL-1β, IL-6, IL-12, IL-18, IFN-γ) and anti-inflammatory (IL-4 and IL-10) cytokine profile were assessed by in vivo, ex vivo and in vitro studies. MOMVs treated mice showed significantly enhanced cytokine production compared to SOMVs treated mice. MOMVs treatment has also upregulated iNOS mRNA synthesis in macrophages. Overall the OMVs of Shigella were found to show a mixed Th1/Th2 response and maintain the balance between pro-inflammation and anti-inflammation in mice. This will be crucial in the development of the next generation OMVs based vaccine against shigellosis.

Serum anti-inflammatory cytokines for the evaluation of inflammatory status in endometriosis

Background:Endometriosis is a frequent gynecologic disease with a severe impact on the quality of life in the affected women; its pathogenesis is yet to be fully understood, with an altered immunity as a possible key factor. The present study aimed to investigate the serum anti-inflammatory cytokine profile in the patients with endometriosis compared with the healthy controls.Materials and Methods:One hundred and sixty women were included, divided into two study groups (Group I — endometriosis; Group 2 — healthy women). We evaluated the serum levels of interleukin-1 receptor antagonist (IL-1Ra), IL-2, IL-2R, IL-4, IL-10, IL-13, and IL-15 with the use of Human multiplex cytokine panels. Statistical analyses (normality distribution analysis, independent t-test, Mann–Whitney U-test) were performed using IBM SPSS software (version 22.0) and GraphPad Prism (version 5.00); receiver operating characteristic curve were used to demonstrate the diagnostic performance of the studied markers.Results:The mean serum level of IL-1Ra, IL-4, and IL-10 were significantly higher in women with endometriosis compared to women free of disease from the control group (30.155, 138.459, and 1.489, respectively, compared to 14.109, 84.710, and 0.688, respectively; P < 0.001, P < 0.001, and P = 0.002, respectively.). No significant differences in the mean serum levels of IL-2, IL-13, and IL-15 were observed between the studied groups and IL-2R had a very low detection rate.Conclusion:Endometriosis is associated with elevated levels of anti-inflammatory cytokines, IL-1Ra, IL-4, and IL-10, markers that have a potential role as a prognostic factor for endometriosis.

45. Examining differences in serum pro- and anti-inflammatory cytokine profiles across behavioral and physical health in healthy adolescent girls

This secondary analysis examined pro- and anti-inflammatory cytokine profiles in healthy adolescent girls to determine whether cytokines vary by behavioral and physical health. Participants ( N = 262) were enrolled in a cohort-sequential study (age groups: 11, 13, 15 and 17 years). We examined mean differences in pro-inflammatory [Interferon-gamma (IFN-γ), Interleukin-1β (IL-1β), IL-6, IL-8, and Tumor Necrosis Factor-alpha (TNF-α)] and anti-inflammatory [IL-4, IL-10, IL-13, IL-5] cytokines across categories of depressive symptoms (Low: Bottom 75%; High: Top 25%), smoking (Non-smokers, Infrequent, Current), and Body Mass Index (normal weight, overweight, obese). Analysis of variance indicated that girls with high depressive symptoms had elevated pro-inflammatory profiles (IFN-γ and IL-6) compared to girls with low symptoms. Non-smokers had higher IL-8 compared to Infrequent or Current smokers. Overweight girls had lower IL-8 compared to normal weight or obese girls. For anti-inflammatory cytokines, girls with low depressive symptoms had higher IL-4 and IL-13 compared to girls with high symptoms. Non-smokers had higher IL-4, IL-10 and IL-5 than Infrequent or Current smokers, and higher IL-13 than Current smokers. Normal weight girls had higher IL-4 compared to obese and overweight girls; overweight girls had higher IL-13 than obese girls. Cytokines, regarded as key regulators of immune functioning, are rarely examined in healthy adolescents. This study illuminates how behavioral and physical health may alter both pro- and anti-inflammatory cytokine profiles in healthy adolescent girls.

Immunoregulatory networks in human Chagas disease

Chagas disease, caused by the infection with Trypanosoma cruzi, is endemic in all Latin America. Due to the increase in population migration, Chagas disease has spread worldwide and is now considered a health issue not only in endemic countries. While most chronically infected individuals remain asymptomatic, approximately 30% of the patients develop a potentially deadly cardiomyopathy. The exact mechanisms that underlie the establishment and maintenance of the cardiac pathology are not clear. However, there is consistent evidence that immunoregulatory cytokines are critical for orchestrating the immune response and thus influence disease development or control. While the asymptomatic (indeterminate) form represents a state of balance between the host and the parasite, the establishment of the cardiac form represents the loss of this balance. Analysis of data obtained from several studies has led to the hypothesis that the indeterminate form is associated with an anti-inflammatory cytokine profile, represented by high expression of IL-10, while cardiac form is associated with a high production of IFN-gamma and TNF-alpha in relation to IL-10, leading to an inflammatory profile. Here, we discuss the immunoregulatory events that might influence disease outcome, as well as the mechanisms that influence the establishment of these complex immunoregulatory networks.