Serum Concentrations Of IL-17A Research Articles

Hypothyroidism impairs the host immune response during the acute phase of Chagas disease

Diseases associated with thyroid hypofunction have been the subject of studies in infectious models, since several authors have demonstrated a pivotal role of iodinated hormones (thyroxine and triiodothyronine) in the modulation of immune effector responses. Using a model of hypothyroidism induced by anti-thyroid drug, we investigated the influence of hypothyroidism in the course of acute Trypanosoma cruzi infection. For this, male Hannover Wistar rats were challenged with methimazole for 21 days (0.02% in drinking water), and water for control counterparts. After confirmation of the hypothyroidism, rats were intraperitoneally challenged with 1x105 blood trypomastigotes of the Y strain of T. cruzi. Our findings suggest that hypothyroidism impairs animal weight gain, but does not affect the health of essential organs. Interestingly, infected hypothyroid animals had a significant increase in thymic cell death, with consequent drop in lymphocyte frequency in whole blood (evaluated on the 11th day of infection). Analyzing the percentage of immune cells in the spleen, we found a strong influence of hypothyroidism as a negative regulator of B cells, and antigenic ability of macrophages (RT1b expression) in the course of the experimental chagasic infection. Enhanced serum IL-17A concentration was induced by T. cruzi infection, but hypothyroidism impaired the production of this mediator as seen in infected hypothyroid animals. Taken together, our work suggests for the first time that hypothyroidism may adversely interfere with the modulation of effective immunity in the early phase of Chagas' disease.

Gut microbiota from androgen-altered donors alter pulmonary responses to ozone in female mice.

In mice, both androgens and the gut microbiota modify pulmonary responses to ozone. We hypothesized that androgens affect gut microbiota and thereby impact pulmonary responses to ozone. To address this hypothesis, we transferred cecal microbiota from male castrated or sham castrated C57BL/6J mice into female germ‐free recipient C57BL/6J mice. Four weeks later mice were exposed to ozone (2 ppm) or room air for 3 hr. The gut microbiomes of castrated versus sham castrated donors differed, as did those of recipients of microbiota from castrated versus sham castrated donors. In recipients, ozone‐induced airway hyperresponsiveness was not affected by donor castration status. However, compared to mice receiving microbiota from sham castrated donors, mice receiving microbiota from castrated donors had elevated numbers of bronchoalveolar lavage (BAL) neutrophils despite evidence of reduced lung injury as measured by BAL protein. Serum concentrations of IL‐17A and G‐CSF were significantly greater in recipients of castrated versus sham castrated microbiota. Furthermore, BAL neutrophils correlated with both serum IL‐17A and serum G‐CSF. Our data indicate that androgen‐mediated effects on the gut microbiota modulate pulmonary inflammatory responses to ozone and suggest a role for circulating IL‐17A and G‐CSF in these events.

Serum levels of selected cytokines [interleukin (IL)-17A, IL-18, IL-23] and chemokines (RANTES, IP10) in the acute phase of immunoglobulin A vasculitis in children

The pathogenesis of the immunoglobulin A vasculitis (IgAV) is still unknown. The available data shows that interleukin (IL)-17, IL-18, IL-23, regulated on activation, normal T cell expressed and secreted (CCL 5, RANTES), and interferon (IFN)-γ-inducible protein 10 (IP10) participate in the pathogenesis of IgAV by influencing the recruitment of leukocytes to the site of inflammation. The aim of this study was to analyze the serum concentration of IL-17A, IL-18, IL-23, RANTES, and IP10 in patients with acute IgAV compared to healthy children. Moreover, we wanted to assess the suitability of the levels of tested cytokines to predict the severity of the disease. All children with IgAV hospitalized in our institution between 2012 and 2017 were included in the study. Cytokines levels were determined in a serum sample secured at admission to the hospital. Basic laboratory tests have also been analyzed. IL-17A, IL-18, and IL-23 were significantly higher in whole IgAV group (52.25 pg/ml; 164.1 pg/ml and 700 pg/ml, respectively) than in the control group (27.92 pg/ml; 140.1 pg/ml and 581.5 pg/ml, respectively). The receiver operating characteristic (ROC) curve analysis revealed the largest area under the curve (AUC 0.979, p < 0.001) for the IL-17A with 95.1% sensitivity and 91.7% specificity. There were no significant differences in cytokine levels depending on the severity of the IgAV. Although the serum levels of the IL-17A, IL-18, and IL-23 increase significantly in the acute phase of the IgAV, they cannot be used as indicators of predicting the course of the disease. IL-17A seems to be a good predictor of IgAV occurrences.

Serum concentrations of IL-17A, IL-17B, IL-17E and IL-17F in patients with systemic sclerosis.

IntroductionImmune system activation, microvascular abnormalities and extracellular matrix deposition in tissues play roles in systemic sclerosis (SSc). Th17 cells producing interleukin (IL)-17 are involved in the pathogenesis of many autoimmune-mediated inflammatory diseases; however, the role of IL-17 in SSc remains unclear.Material and methodsThe concentrations of IL-17A, IL-17B, IL-17E, and IL-17F in the serum of patients with SSc and in the healthy control group were assessed with regard to type of the disease – whether limited (lSSc) or diffuse (dSSc) – and symptoms.ResultsNo difference was found between patients with SSc and the control group as regards the serum concentration of IL-17A. However, IL-17B and IL-17E levels in patients with SSc, and its types diffuse and limited were higher (p < 0.001) compared to the control. The serum level of IL-17F was higher in SSc (p < 0.005) and lSSc (p < 0.05) compared to the control. Serum concentration of IL-17B was elevated in SSc patients with renal abnormalities (p < 0.05) compared to those without. Serum levels of IL-17B correlated with the levels of IL-17E in patients with SSc (r = 0.54, p < 0.05).ConclusionsIncreased synthesis of IL-17B, IL-17E and IL-17F appears to play a role in the pathogenesis of SSc, in contrast to IL-17A. Higher levels of IL-17B and IL-17E are associated with the development of both lSSc and dSSc, whereas IL-17F is associated with lSSc only. Further studies are needed to elucidate their role in the pathogenesis of the disease.

Mucosal Immunity Related to FOXP3+ Regulatory T Cells, Th17 Cells and Cytokines in Pediatric Inflammatory Bowel Disease.

BackgroundWe aimed to investigate mucosal immunity related to forkhead box P3 (FOXP3+) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD).MethodsMucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-RORγt antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon (IFN)-γ, soluble CD40L, and tumor necrosis factor-α.ResultsFOXP3+ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. RORγt+ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 (9.6 ± 1.5 vs. 12.7 ± 3.0), IL-21 (14.9 ± 1.5 vs. 26.4 ± 9.1), IL-33 (14.3 ± 0.9 vs. 19.1 ± 5.3), and IFN-γ (15.2 ± 5.9 vs. 50.2 ± 42.4) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 (119.1 ± 79.6 vs. 52.9 ± 39.1) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A (64.2 ± 17.2 vs. 28.3 ± 10.0) and IL-22 (37.5 ± 8.8 vs. 27.2 ± 3.7) were significantly higher in ulcerative colitis than those in Crohn's disease.ConclusionMucosal immunity analysis showed increased FOXP3+ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.

Serum concentrations of interleukin-17A but not interleukin-17F are elevated in children with recent-onset Hashimoto's thyroiditis

Background: Recent advances in immunology suggest that T-helper 17 lymphocytes (Th17) have a major role in the disrupted autoimmunity in Hashimoto's thyroiditis (HT). However, there are no data on the Th17 characteristics, especially regarding the dominant interleukins (ILs) that they produce in children with HT. Material and Methods: With an aim to determine the role of two major Th17 cytokines in children with HT, we measured serum concentrations of IL-17A and IL-17F in 40 children with recent-onset HT and 40 age- and sex-matched controls by enzyme-linked immunosorbent assay. Results: Serum IL-17A concentrations were significantly higher in children with HT when compared to controls (3.39 ± 6.93 pg/mL vs. 0.12 ± 0.47 pg/mL, P = 0.00). However, the IL-17F concentrations were similar in patients and the controls (11.12 ± 15.34 pg/mL vs. 9.68 ± 12.87 pg/mL, P = 0.65). Conclusions: The elevated concentrations of IL-17A, one of the major effector cytokines of the Th17 system, suggest its possible role in the pathogenesis of HT in children.

Interleukin 17A gene polymorphism rs2275913 is associated with osteitis after the Bacillus Calmette-Guérin vaccination.

Interleukin-17 (IL-17) appears to promote the host's defence against mycobacterial infections. This study evaluated the association between IL17A gene polymorphism and the risk of Bacillus Calmette-Guérin (BCG) osteitis after newborn vaccination and between IL17A gene polymorphism and IL-17A concentrations in serum. IL17A rs2275913 gene polymorphisms and serum IL-17A concentrations were studied in 132 adults aged 21-49 years from across Finland, who had BCG osteitis in infancy after a newborn BCG vaccination. The subjects were recruited in 2007-2008, and their whole-blood samples were sent to the National Institute for Health and Welfare, Turku, Finland. Their genotypes and minor allele frequencies were compared with 405 population-based unvaccinated controls aged two to three months from a prospective birth cohort study. The genotypes and allele frequencies of IL17A rs2275913 differed significantly between the former BCG osteitis patients and controls. The genotype was variant in 75.8% of cases and 64.0% of controls (p = 0.012), and the minor allele frequency was 50.0% in the cases and 41.6% of the controls (p = 0.009). Serum IL-17 concentrations did not differ significantly between the cases with wild or variant genotypes. IL17A rs2275913 gene polymorphism was associated with a risk of BCG osteitis after vaccination.

Assessment of Th17 lymphocytes and cytokine IL‑17A in epithelial ovarian tumors.

The present study was carried out to assess the percentage of T helper 17 (Th17) lymphocytes in blood and tissue and IL-17A serum concentrations in patients with epithelial ovarian tumors. Two isoforms, IL-17A and IL-17F, as well as IL-21 and IL-22, were simultaneously investigated. The study group consisted of 60women affected by epithelial ovarian tumors (benign, borderline and malignant) and 20women without ovarian pathology as a control group. The evaluation of the percentage of Th17 cells secreting IL-17A, IL-17F, IL-21 and IL-22 in peripheral blood and tumor tissues was performed using flow cytometry applying a Th17 cytokine staining panel. The blood serum concentration of IL-17A was determined using ELISA. We found no statistically significant differences in the subpopulations of Th17 lymphocytes, either in peripheral blood or in ovarian tissues, following comparison of the women with and without ovarian pathology. Negative correlations were found between the percentage of CD4+/IL-21+ (rs=0.8, p=0.02) and CD4+/IL-17+ (rs=-0.78, p=0.03) in the tissue and IL-17A in blood serum in the group of patients with borderline ovarian tumors. A negative correlation was also found between IL-17A and the percentage of CD4+/IL-21+ in peripheral blood (rs=‑0.48, p=0.03) in the group of patients with ovarian cancer. The increased percentage of Th17 cells in tissue was not correlated with the overall survival of the ovarian cancer patients. In conclusion, we showed that more Th17 cells secreted IL-17A and IL-21 in the tissue of borderline ovarian tumors and less IL-17A in serum. We also observed that in peripheral blood of the patients with ovarian cancer, there was a higher percentage of Th17 lymphocytes and a lower concentration of IL-17A in serum indicating a negative correlation. An increased percentage of Th17 cells in ovarian tissue does not influence the time of survival of patients with ovarian cancer.

A possible association of baseline serum IL-17A concentrations with progression-free survival of metastatic colorectal cancer patients treated with a bevacizumab-based regimen

BackgroundColorectal cancer is a major public health issue worldwide. Interleukin-17 (IL-17) and Th17 (T-helper cell type 17)-related molecules are involved in tumor development and in resistance to bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody used in association with chemotherapy in metastatic colorectal cancer. Some studies have previously shown that IL-17A and IL-17F polymorphisms, respectively rs2275913 and rs763780, are associated with gastric or colorectal cancer risk. Here we aimed at studying the influence of IL-17A-related individual factors on overall survival and progression-free survival in patients with metastatic colorectal cancer treated with a bevacizumab-based chemotherapy.MethodsPre-treatment serum biomarkers were retrospectively evaluated in 122 metastatic colorectal cancer patients treated by bevacizumab in combination with chemotherapy at 2-weeks intervals in a prospective cohort study (NCT00489697). The polymorphisms of IL-17A and IL-17F were analyzed by polymerase chain reaction - restriction fragment length polymorphism. Serum concentrations of Th17-related cytokines were measured by MultiPlex. The impact of individual parameters on overall survival and progression-free survival was assessed using multivariate Cox models.ResultsHigh baseline IL-17A serum concentrations were significantly associated with shorter progression-free survival [p = 0.043]. Other baseline serum Th17-related cytokines and polymorphisms of IL-17 were not associated with overall survival or progression-free survival.ConclusionsIn this ancillary study, baseline serum IL-17A concentration is the only Th17/IL-17 related factor that was significantly associated with the response of patients with metastatic colorectal cancer to bevacizumab. But this main significant result is highly dependent on one case which, if left out, weakens the data. Other clinical studies are required to confirm this association.Trial registrationNCT00489697. June 20, 2007.

Circulating T-helper 17 cells and associated cytokines in psoriasis.

Recently, a new population of IL-17-producing CD4 T helper (Th) cells, named Th17, was identified and shown to be involved in various inflammatory and autoimmune diseases, including psoriasis. To determine the frequency of Th17 cells and related cytokines in peripheral blood of patients with psoriasis, and to analyse their association with disease severity. This was a prospective study comprising 34 patients with psoriasis and 24 healthy controls. Clinicoepidemiological details of patients were recorded, and severity of psoriasis was assessed by means of the Psoriasis Area and Severity Index. Circulating Th1 and Th17 cells in untreated patients with psoriasis and healthy controls were quantified by flow cytometry. In sera collected from patients with psoriasis and healthy controls, concentrations of IL-17A and IL-23 were examined by ELISA. Increased frequencies of CD4+ IL-17A+ T cells were seen in peripheral blood of patients with psoriasis vulgaris (P < 0.001). Although serum IL-17A and IL-23 concentrations were higher in patients with psoriasis than in controls, the results did not reach statistical significance. We could not find any correlation between the studied T cells or related cytokines and the disease severity. Increased serum levels of circulating Th17 cells and related cytokines may contribute to the cutaneous pathology of psoriasis, as well as the inflammatory process that is a hallmark of psoriasis.

Abstract 2241: Serum and plasma IL-17A concentrations in lung cancer patients and controls

Abstract Purpose: IL-17A, a cytokine produced by Th17 cells, is reportedly a central regulator of lung tumor growth (Reppert et al., OncoImmunology 1, 2012) and a potential serum biomarker for lung cancer (Xu et al., Biomarkers, 2014). Serum concentrations of IL-17A are too low to measure in most samples (on the order of 0.1 pg/mL) using commercially available ELISAs. In order to overcome this limitation, we developed the S-PLEX™ Human IL-17A ultrasensitive assay which is capable of accurately measuring IL-17A in serum and plasma. We used this assay to measure IL-17A concentrations in serum samples from lung cancer patients and controls. Methods: Serum samples from 59 lung cancer patients and 44 apparently healthy controls (including 14 heavy smokers) were analyzed using S-PLEX technology to determine IL-17A concentrations. In addition, IL-17A concentrations were measured in matched plasma samples from 24 of the controls. S-PLEX is a new ultrasensitive immunoassay format based on MSD's MULTI-ARRAY® electrochemiluminescence technology. The IL-17A assay requires only 25 μL of serum or plasma per measurement and can be run on the MESO® SECTOR S 600 and MESO QuickPlex® SQ 120 instruments. Results: The S-PLEX Human IL-17A assay was capable of accurately measuring IL-17A concentrations in 125 of the 127 samples tested. The lower limit of detection was 6 fg/mL and the assay range (LLOQ to ULOQ) was from 20 fg/mL to 200,000 fg/mL. Typical intra-plate coefficients of variation (CVs) ranged between 5% and 15%. Control samples run at 3 levels, in multiple replicates over multiple days, produced CVs &amp;lt;20%. Spike recovery and dilution linearity were between 80% and 120%, and IL-17A levels in matched serum and plasma samples were similar. Specificity of the assay was demonstrated by analyte depletion using several anti-IL-17A specific antibodies, indicating the assay is specific for the IL-17A homodimer. There was no detectable cross-reactivity to the IL-17F homodimer, and the IL-17A/F heterodimer cross-reactivity was less than 1%. In this study, IL-17A serum concentrations were not found to be significantly different between lung cancer patients and controls, with a median concentration of 183 fg/mL and interquartile range (IQR) of 88-369 fg/mL (n = 59) for lung cancer patients, compared to 128 fg/mL with an IQR of 75-198 fg/mL (n = 44) for controls. Conclusion: We have developed a highly specific and sensitive IL-17A assay that is 100 times more sensitive than the current limits of ELISA technology. This assay enables accurate determination of IL-17A concentrations in serum and plasma samples from lung cancer patients and healthy controls. The results from this study do not support the use of IL-17A as an effective serum biomarker for the presence of lung cancer. Citation Format: Animesh Shukla, Sheldon Grove, Simone Barbero, Galina N. Nikolenko, Anu Mathew, Martin K. Stengelin, Eli N. Glezer, Jacob N. Wohlstadter. Serum and plasma IL-17A concentrations in lung cancer patients and controls. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2241.

Expression of IL-17A concentration and effector functions of peripheral blood neutrophils in food allergy hypersensitivity patients

Lymphocytes Th17 and other types of immune system cells produce IL17. By induction of cytokines and chemokines, the IL17 cytokine is involved in mechanisms of allergic reaction with participation of neutrophil granulocytes. It affects activation, recruitment, and migration of neutrophils to the tissues, regulating inflammatory reaction intensity. Excited neutrophils secrete inter alia elastase and reactive oxygen species (ROS)--significant mediators of inflammation process responsible for tissues damage.The aim of the study was to evaluate the concentrations of serum interleukin 17A, serum neutrophil elastase, and ROS production by neutrophils in patients with food allergy.The study included 30 patients with food allergy diagnosed based on interview, clinical symptoms, positive SPT, placebo controlled double-blind oral provocation trial, and the presence of asIgE in blood serum against selected food allergens using fluoro-immuno-enzymatic method FEIA UNICap 100. The control group consisted of 10 healthy volunteers. The concentrations of IL17A were determined in all patients using ELISA method with eBioscience kits, and elastase using BenderMed Systems kits. Chemiluminescence of non-stimulated neutrophils was evaluated using luminol-dependent kinetic method for 40 min on Luminoskan (Labsystems luminometer).The results of serum IL-17A concentrations and the values of chemiluminescence obtained by non-activated neutrophils, as well as elastase concentrations, were higher in patients with food allergic hypersensitivity compared to healthy volunteers.This study demonstrates a significance of IL-17A and activated neutrophil granulocytes in the course of diseases with food allergic hypersensitivity.

Abstract 176: Interleukin 17 A, Hepatosplenic Mansonic Schistosomiasis and Atherosclerosis

Introduction: The immune system plays an important role in the pathophysiology of schistosomiasis and atherosclerosis due to its activation of various immune cells and release of different inflammatory mediators. However, the pathologies of these diseases are not fully understood. The main aim of this study was to detect atherosclerotic disease in patients with mansonic schistosomiasis, while the secondary objectives were evaluate the serum concentrations of interleukin 17A (IL 17 A) and 22 (IL 22). Hypothesis: Atherosclerosis is not common in patients with mansonic schistosomiasis. Methods: This study included 30 patients (14 men, 16 women; mean age = 59.87 ± 7.50 years) with hepatosplenic mansonic schistosomiasis that agreed to participate in the study by signing the Free and Informed Consent Form. Ten healthy volunteers (four men, six women) were selected as controls for interleukin concentrations. Atherosclerosis was evaluated by measuring the carotid artery intima-media thickness (IMT ≥1.5 mm are indicative of atherosclerotic plaques). Shapiro-Wilk test was necessary to determine whether the variables followed a normal distribution. The continuous variables were evaluated using student’s t test. P value ≤ 0.05 was considered statistically significant. Results: The main clinical characteristics of the patients were as follows: benign arrhythmias, 19 patients (63%); hypertension, 17 (56%); smoking, 12 (40%); hepatitis B or C, nine (30%); peripheral vascular insufficiency, nine (30%); family history of CAD, nine (30%); diabetes mellitus, one (3.3%); leukemia, one (3.3%); and non-cardiac surgery, 24 (80%). There were no differences in the IL 17 A concentrations (15.63 ± 0.00 pg/ml vs 15.63 ± 0.00 pg/ml, p = 1) and in the IL 22 concentrations (7.81 ± 0.00 pg/ml vs 7. 81 ± 0.00 pg/ml, p = 1) between patients and controls. The overall mean of the intimal medial thickness was 0.7 ± 0.2 mm Conclusions: None of patients had atheroma. The serum concentrations of IL 17A and IL 22 were equal between patients and controls (concentrations undetectable or low). It is possible that the immune response of patients with hepatosplenic mansonic schistosomiasis may attenuate the development of atherosclerosis.

IL23R gene polymorphism with juvenile idiopathic arthritis and its association with serum IL-17A.

Interleukin 23 (IL-23) and its receptor (IL-23R) seem to play a major role in differentiation of CD4+ T cells into Th17 cells, induction of IL-17 production, and activation of inflammatory pathways. Recent studies have suggested the association of IL-23R polymorphisms with bone and articular inflammation in diseases such as ankylosing spondylitis and rheumatoid arthritis. The aim of this study was to determine the association between IL-23R polymorphisms and juvenile idiopathic arthritis (JIA). A case-control study on 55 patients with JIA and 78 healthy controls was performed. All samples were genotyped for eight single nucleotide polymorphisms (SNPs) of IL23R (rs1004819, rs2201841, rs10889677, rs1495965, rs7517847, rs10489629, rs11209026 and rs1343151), using real-time polymerase chain reaction Taqman genotyping technique. Forty-two patients and 42 healthy controls were chosen randomly to measure the level of serum IL-17A using enzyme-linked immunosorbent assay. Although the heterozygous genotype of rs1004819 (GA) showed a weak, but statistically significant protective effect on polyarticular subtype (P=0.03), none of the selected SNPs were associated with JIA overall. Indeed the analysis of haplotypes did not show any significant association with JIA. Serum IL-17A level was not significantly different among patients and healthy controls and between JIA subtypes, as well. Moreover, there was no significant correlation between SNPs and serum IL-17A concentration. This is the first study of the IL-23R gene in Iranian patients with JIA. Our results did not show any strong association between IL-23R polymorphisms and JIA disease or serum IL-17A levels. The only association was seen between rs1004819 and polyarticular JIA. Further larger studies may help clarify the role, if any, of the IL-23/IL-17 pathway in the pathogenesis of JIA.

Up-regulated integrinα4β1 on systemic lymphocytes and serum IL-17A in interstitial pneumonia.

In interstitial pneumonia (IP), lymphocytes play an important role in lung injury and the involvement of integrinα4β1 on leukocytes has previously been reported in animal models. Although the integrinα4β1 expression level is known to be up-regulated by inflammatory cytokines, the involvement of interleukin (IL)-17A is unclear. The purpose of this study is to address the possible involvement of integrinα4β1 on circulating lymphocytes and its correlation with serum IL-17A in interstitial lung diseases (ILDs). We measured the expression levels of integrinα4β1 on peripheral lymphocytes and the serum concentration of IL-17A and IL-23 in subjects with ILDs (n = 27; 14 males and 13 females, 66.7 ± 7.8 years old) and control subjects (n = 10; 5 males and 5 females, 66.6 ± 4.6 years old). Recombinant IL-17A up-regulated expression levels of integrinα4β1 on healthy human lymphocytes in an in vitro experiment. Expression levels of integrinα4β1 were significantly higher in those with acute hypersensitivity pneumonitis (HP) and non-specific IP (NSIP) compared with control. Serum IL-17A concentration was also significantly increased in acute HP and NSIP subjects compared with control. And IL-17A concentration positively correlated with integrinα4β1 expression level (P < 0.05). Serum IL-23 was below the minimal detectable level in all subjects. These findings suggest that up-regulated levels of integrinα4β1 on systemic lymphocytes and elevated serum IL-17A might be involved in the extravasation of lymphocytes in IP.

The TH17/Treg Imbalance in Rheumatoid Arthritis and Relation to Disease Activity

Objectives: T regulatory cells (Treg) and proinflammatory TH17 cells are newly identified T lymphocyte subsets, which have significant effects on autoimmunity and inflammation. Tregs play key role in the maintenance of self-tolerance. TH17/Treg disturbed balance has been reported to contribute to several autoimmune diseases.Our aim was to assess the Treg/TH17 pattern and TH17 related cytokines, in peripheral blood of Egyptian rheumatoid arthritis patients, and their relation to disease activity score (DAS). Analyzing IL17A and IL23 as indicators of TH17 function, was to study the effect of TH17 in RA.Methods: 100 Egyptian rheumatoid arthritis patients, divided into Group I (14), Group II (48), Group III (38), with low 5.1, activity DAS score respectively; and 50 healthy age and sex matched controls were enrolled. Peripheral blood TH17 and Treg (CD4+CD25+Foxp3+) frequencies were analyzed by flowcytometry, and the serum levels of interleukins (IL17A), (IL23) were determined by ELISA.Results: Active RA patients (groups II and III) revealed an obvious increase in peripheral TH17 frequencies, and levels of TH17-related cytokines, and a significant decrease in Treg (CD4+CD25+Foxp3+) frequencies in group III, when compared to healthy controls. TH17/Treg ratios were positively correlated with serum concentrations of IL17A and IL23 cytokines. Frequencies and levels showed statistical significant correlation with DAS scoring.Conclusions: Our study indicated that TH17/Treg balance was disturbed in peripheral blood of RA patients, leading to an increase of proinflammatory cytokines, correlating with DAS, and suggesting an important role in the development of RA.

Th-17 related regulatory network in the pathogenesis of Arab patients with systemic lupus erythematosus and lupus nephritis.

The present study aimed to identify the genes involved in the pathogenesis of systemic lupus erythematosus (SLE) in Arabs by investigating a panel of 84 genes related to the t helper (Th)17-related regulatory network and to further explore the expression levels of serum interleukin (IL)-17A and IL-17F in a studied cohort. A comparative analysis of gene expression profile in SLE and lupus nephritis (LN) patients against that of healthy controls (HC) was performed. A quantitative real-time polymerase chain reaction (PCR) (Th17 autoimmunity and inflammation) array analysis was performed in peripheral white blood cells of 66 SLE patients under specific medical treatment and 30 age/gender/ethnically matched healthy controls. Statistical analysis was carried out using the RT(2) Profiler TM PCR Data Analysis tool. The analysis of Th17 pathway revealed 14 genes (IL-17A, IL-17C, IL-17D, IL-17F, IL-18, IL-12RB2, IL-23R, CCL2, CCL20, CXCL5, MMP3, RORC, STAT4 and TRAF6) that are differentially expressed in SLE and HC (fold change [FC]<2, P<0.0006). No significant difference in expression profiles was observed between SLE and LN. A significant difference in serum concentration of IL-17A (P=0.002) and IL-17F (P=0.002) was observed between SLE (13.91±4.25) and LN (18.26±4.24). Our study is the first to investigate a panel of 84 genes related to Th17 regulatory pathway in Arab SLE subjects and the first to explore the effect of current immunosuppression regimens on Th17 regulatory pathway. It paves the way for understanding the etiology of SLE and autoimmune diseases in general.

Changes of serum cytokines-related Th1/Th2/Th17 concentration in patients with postmenopausal osteoporosis

Background: Postmenopausal osteoporosis is now hypothetically considered to be an autoimmune and inflammatory process in which many pro-inflammatory and T cell-derived cytokines play important roles in the loss of bone mass. For instance, interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) secreted by Th1 and IL-6, IL-4, and IL-10 secreted by Th2 have been shown to be involved in the pathogenesis of osteoporosis. Interleukin-17 (IL-17) is a characteristic cytokine secreted by Th17 cells of the CD4 + subgroup. Although IL-17 has been shown to enhance bone resorption in ovariectomized mouse model, bone cells and genetic research, human-related studies of IL-17 are few.Methods: According to WHO classification of osteoporosis by the T scores of BMD, the subjects were divided into the postmenopausal osteoporosis group (T scores≤−2.5), the postmenopausal osteopenia group (−2.5 < T scores<−1), and the postmenopausal normal BMD group (T scores≥−1); 30 subjects in each group. Cytometric bead array (CBA) technique was employed for serum determination of the primary indexes including IL-17A, IL-2, IFN-γ, TNF-α, IL-6, IL-4, and IL-10 concentrations in the 90 volunteers. In the meantime, serum calcium, phosphorus, magnesium, and alkaline phosphatase concentrations were also determined in the patients. One-way analysis of variance (one-way ANOVA) was employed in data analysis to determine whether the testing results of various parameters had significant differences. The bivariate correlation was tested with the Pearson correlation coefficient. When p < 0.05, the difference was considered to have statistical significance.Results: Serum IL-17A concentration was significantly higher in the postmenopausal osteoporosis group than in the postmenopausal osteopenia group and the postmenopausal normal BMD group, but the difference between the postmenopausal osteopenia group and the postmenopausal normal BMD group had no statistical significance. IL-17A was negatively correlated with BMD. To our knowledge, we discovered for the first time that serum concentrations of IFN-γ and IL-4 were significantly lower in the postmenopausal osteoporosis group than in the postmenopausal normal BMD group; IFN-γ and IL-4 were positively correlated with BMD. In addition, we also determined that BMI was negatively correlated with BMD; IL-17A was positively correlated with serum calcium. However, no significant differences in IL-6, TNF-α, IL-2, and IL-10 were observed among the three groups; these three factors were not correlated with BMD.Conclusions: Our experiments have confirmed the roles of IL-17 in the pathogenesis of postmenopausal osteoporosis and in the promotion of bone resorption. Targeted therapy of IL-17, IFN-γ, and IL-4 may be beneficial in the treatment of patients with postmenopausal osteoporosis. Our experiments have also confirmed the roles of IFN-γ and IL-4 in the pathogenesis of postmenopausal osteoporosis and in the inhibition of bone resorption.

Dioxin-Like Chemicals Exposure Leads to an IL-22-Related Autoimmune Trait in Human

Dioxin-Like Chemicals Exposure Leads to an IL-22-Related Autoimmune Trait in HumanAbstract Number:2092 Nian-wei Lee*, Yue-liang Guo Nian-wei Lee* National Taiwan University Hospital Department of Environmental and Occupational Medicine, Taiwan, E-mail Address: [email protected] Search for more papers by this author and Yue-liang Guo National Taiwan University Hospital Department of Environmental and Occupational Medicine, Taiwan, E-mail Address: [email protected] Search for more papers by this author AbstractBackground: Over 2000 Taiwanese ingested cooking rice oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in 1979. A Yucheng (‘oil-disease’ in Chinese) registry was established for long-term follow-up, including 1991 exposed subjects. A highly-increased mortality of systemic lupus erythematosus (SLE) was observed in the exposed women starting 10 years after the exposure. This study determined whether serum markers of autoimmunity were related to dioxin-like chemicals (DLCs) exposure.Methods: A total of 24 Yucheng women and 48 age/neighborhood-matched referent women, both without clinical SLE, donated blood for this study. Serum interleukin (IL)-17A, IL-22, IL-4, interferon (IFN)-gamma, and antinuclear antibody (ANA) were measured.Results: Serum IL-17A level was mildly elevated in Yucheng women (mean±standard deviation, 18.1±6.8 pg/ml) compared to referents (14.4±5.3 pg/ml; p=0.03), whereas serum IL-22 level was significantly higher in Yucheng women (65.7±32.3 pg/ml) than in referents (32.4±11.1 pg/ml; p<0.0001). No differences were observed in IL-4 and IFN-gamma. Serum IL-22 level was further found to be positively correlated with serum total toxic equivalent (TEQ) in Yucheng women (R squared=0.64, p<0.0001). Serum concentration of IL-17A and total TEQ were uncorrelated in Yucheng women (R squared=0.04, p=0.37). In addition, a higher percentage of Yucheng women (71%) had elevated serum ANA compared to referents (33%; p=0.002). While Yucheng and referent women were divided respectively into two groups, ANA (-) and ANA (+) [ANA (-): ANA titer<40 (+); ANA (+): ANA titer≥1:40 (+)], serum IL-22 level was highest in Yucheng women with ANA (+) (p<0.0001).Conclusion: IL-22-secreting, aryl hydrocarbon receptor-bearing T helper cells seem to play a key role in the DLC-triggering autoimmune trait.

Serum cytokines as biomarkers for age-related macular degeneration

This study evaluates the potential of serum pro-inflammatory cytokines as AMD biomarkers. Serum samples from 30 age-related macular degeneration (AMD) patients and 15 age-matched controls were examined for 16 inflammatory cytokines using multiplex ELISA. Patients were divided into three subgroups (improvement/no change/deterioration during anti-VEGF treatment) by OCT and funduscopy, and correlated to the cytokine levels. Serum concentrations of IL-1α, IL-1β, IL-4, IL-5, IL-10, IL-13, and IL-17 were significantly higher in AMD patients than in controls. None of the co-variables expressed a significant effect on the tested cytokines. Only IL-1a and IL-17 showed a statistically significant difference between groups (improved, unchanged, deteriorated) as determined by one-way ANOVA. Patients with increased macular thickness during treatment showed significantly lower levels of IL-17 compared to improved cases and to unchanged cases (p =0.004, 0.03 respectively, Dunnett's T3 post hoc multiple test). TNF-α was significantly higher in improved cases compared to deteriorated cases (p =0.03, Dunnett's T3 post hoc multiple test). IL-17 was a significant predictor for macular oedema using linear regression (β = -0.888, p <0.05). Elevation of IL-1α, IL-1β, IL-4, IL-5, IL-10, IL-13, and IL-17 in the serum of AMD patients supports the hypothesis of AMD as an inflammatory disease. Patients with high IL-17 and TNF-α serum levels were more likely to have a favourable course under VEGF therapy. These cytokines may be used as easy-to-obtain biomarkers.