Serum interleukin-17A Levels Research Articles

Interleukin 6 and interleukin 17A serum levels and gene- polymorphisms in the development of early allograft rejection in living donor liver transplant recipients

The aim of this study is to evaluate the role of serum level of Interleukin 6(IL-6) and Interleukin 17 (IL-17) in liver transplantation outcome for living recipients, Analyze the relation between the gene polymorphism and the occurrence of rejection after liver transplantation and Study the relation between the gene polymorphism and the occurrence of different infectious complications. The study was conducted in March 2023 and included 60 healthy volunteers from the National Liver Institute (NLI) blood bank at Menoufia University and 120 live donation liver recipient patients at NLI. During one month of liver transplantation, the cytokine levels (IL-17, IL-6 proteins, IL-6 G-174C, and IL-17 A rs2275913 gene polymorphism) and CD4 levels for 60 patients of 120 live donation liver recipient patients whom early reject transplanted tissue and the same parameters were measured after 6 months follow up for non-reject group. The main finding of this study was that the post-transplant rejection group and the post-transplant non-rejection and control groups differed significantly in the genotype frequency (CC, CG, and GG) or alleles of IL-6 G-174C (p = 0.011). On the other hand IL-17A rs2275913 gene polymorphism and its alleles (p = 0.71) showed no statistically significant difference. We also observed that serum IL-17 levels, with 100% specificity and 100% sensitivity threshold, will be more sensitive and specific than serum IL-6 and CD4 count in differentiating post-transplant rejection from non-rejection patients. The results showed that there was no significant relationship between the genotypes and serum levels of interleukins and the type and degree of rejection. Proinflammatory cytokines might be useful indicators for distinguishing and early identifying unfavorable outcomes after transplantation, allowing for prompt and effective treatment intervention. To evaluate these findings, prospective clinical trials are required.

Altered serum interleukin-17A and interleukin-23A levels may be associated with the pathophysiology and development of generalized anxiety disorder

In recent times, the pathogenesis of generalized anxiety disorder (GAD) and the influence of pro- and anti-inflammatory cytokines on it have garnered considerable interest. Cytokine research, especially Th-17 cytokine research on GAD patients, is limited. Here, we aim to assess the role of interleukin-17A (IL-17A) and interleukin-23A (IL-23A) in the pathophysiology and development of GAD. This investigation included 50 GAD patients and 38 age-sex-matched healthy controls (HCs). A psychiatrist diagnosed patients with GAD and assessed symptom severity using the DSM-5 and the GAD-7 scales. The serum concentrations of IL-17A and IL-23A were determined using commercially available ELISA kits. GAD patients exhibited elevated levels of IL-17A (77.14 ± 58.30 pg/ml) and IL-23A (644.90 ± 296.70 pg/ml) compared to HCs (43.50 ± 25.54 pg/ml and 334.40 ± 176.0 pg/ml). We observed a positive correlation between disease severity and cytokine changes (IL-23A: r = 0.359, p = 0.039; IL-17A: r = 0.397, p = 0.032). These findings indicate that IL-17A and IL-23A may be associated with the pathophysiology of GAD. ROC analysis revealed moderately higher AUC values (IL-23A: 0.824 and IL-17A: 0.710), demonstrating their potential to discriminate between patients and HCs. Also, the sensitivity values of both cytokines were relatively higher (IL-23A: 80.49% and IL-17A: 77.27%). According to the present findings, there may be an association between peripheral serum levels of IL-17A and IL-23A and the pathophysiology and development of GAD. These altered serum IL-17A and IL-23A levels may play a role in directing the early risk of developing GAD. We recommend further research to ascertain their exact role in the pathophysiology and their performance as risk assessment markers of GAD.

Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis.

Autoimmune Thyroiditis (AIT) is the most common thyroid disease; however, there were no measures to prevent the progression of the disease. The present study attempts to identify that Notch signaling regulates the differentiation of T helper 17 (Th17) cells by activating downstream Phosphatidylinositol-3 kinase/protein kinase/mechanistic target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathway participating in the thyroid injury of the experimental autoimmune thyroiditis (EAT). In vivo experiments, mice were randomly divided into 4 groups: a control group, an EAT group, and two groups with LY294002 treatment (pTg plus 25mg/kg or 50mg/kg LY294002, respectively). The degrees of thyroiditis were evaluated, and the percentage of Th17 cells, expression of interleukin-17A (IL-17A), and the main components of the Notch-PI3K signaling pathway were detected in different groups. In vitro experiments, two different dosages of LY294002 (25 and 50μM) were used to intervene splenic mononuclear cells (SMCs) from EAT mice to further evaluate the regulatory effect of Notch-PI3K pathway on Th17 cells. Our data demonstrate that the infiltration of Th17 cells and the expressions of IL-17A, Notch, hairy and split 1 (Hes1), p‑AKT (Ser473), p‑AKT (Thr308), p‑mTOR (Ser2448), S6K1, and S6K2 increased remarkably in EAT mice. After PI3K pathway was blocked, the degrees of thyroiditis were significantly alleviated, and the proportion of Th17 cells, the expression of IL-17A, and the above Notch-PI3K pathway-related molecules decreased in a dose-dependent manner. Additionally, the proportion of Th17 cells was positively correlated with the concentration of serum thyroglobulin antibody (TgAb), IL-17A, and Notch-PI3K pathway-related molecules mRNA levels. Notch signal promotes the secretion of IL-17A from Th17 cells by regulating the downstream PI3K/AKT/mTORC1 pathway through Hes-Phosphatase and tensin homolog (PTEN) and participates in thyroid autoimmune damage, and the PI3K pathway inhibitor may play important effects on AIT by affecting Th17 cells differentiation.

Evaluation of Interleukin-17 A Levels in Patients with Breast Carcinoma

Breast cancer is a highly common form of cancer that impacts a considerable proportion of women on a global scale. Interleukin 17A (IL-17A) is a cytokine that has both anti-tumor and pro-tumor effects, which can vary depending on the specific tumor microenvironment. The aim of this study was to determine whether IL-17A can be used as a biomarker for diagnosis of breast cancer. Therefore, we compared concentrations of serum IL-17A in patients suffering from breast carcinoma and normal control women by an enzyme-linked immunosorbent assay (ELISA). This study included 86 women, 44 patients that were diagnosed with breast carcinoma, and 42 normal control women. Serum IL-17A levels in both case and control groups were measured by sandwich ELISA kits. The IL-17A serum level was significantly higher among patients with breast carcinoma than in the control group (p<0.001). The serum IL-17A concentration was significantly higher in estrogen receptor-positive cases than in estrogen receptor-negative cases (p=0.033). The highest levels of IL-17A were detected in patients with stage 2 breast carcinoma rather than stage 3 with no significant correlation. There was no correlation between IL-17A level and tumor size, lymph node invasion, or metastasis in patients with breast cancer. In conclusion, a high level of IL-17A in breast carcinoma patients compared to the control group was detected in our study. It indicates that IL-17A could be a promising biomarker for diagnosis of breast cancer and may play a role in tumor development. High levels of IL-17A were not a predictor of poor prognosis in breast cancer patients as it was not related to tumor size, lymph node invasion, or metastasis.

Protective role of IL-17-producing γδ T cells in a laser-induced choroidal neovascularization mouse model

BackgroundVision loss in patients with wet/exudative age-related macular degeneration (AMD) is associated with choroidal neovascularization (CNV), and AMD is the leading cause of irreversible vision impairment in older adults. Interleukin-17A (IL-17A) is a component of the microenvironment associated with some autoimmune diseases. Previous studies have indicated that wet AMD patients have elevated serum IL-17A levels. However, the effect of IL-17A on AMD progression needs to be better understood. We aimed to investigate the role of IL-17A in a laser-induced CNV mouse model.MethodsWe established a laser-induced CNV mouse model in wild-type (WT) and IL-17A-deficient mice and then evaluated the disease severity of these mice by using fluorescence angiography. We performed enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS) to analyze the levels of IL-17A and to investigate the immune cell populations in the eyes of WT and IL-17A-deficient mice. We used ARPE-19 cells to clarify the effect of IL-17A under oxidative stress.ResultsIn the laser-induced CNV model, the CNV lesions were larger in IL-17A-deficient mice than in WT mice. The numbers of γδ T cells, CD3+CD4+RORγt+ T cells, Treg cells, and neutrophils were decreased and the number of macrophages was increased in the eyes of IL-17A-deficient mice compared with WT mice. In WT mice, IL-17A-producing γδ T-cell numbers increased in a time-dependent manner from day 7 to 28 after laser injury. IL-6 levels increased and IL-10, IL-24, IL-17F, and GM-CSF levels decreased in the eyes of IL-17A-deficient mice after laser injury. In vitro, IL-17A inhibited apoptosis and induced the expression of the antioxidant protein HO-1 in ARPE-19 cells under oxidative stress conditions. IL-17A facilitated the repair of oxidative stress-induced barrier dysfunction in ARPE-19 cells.ConclusionsOur findings provide new insight into the protective effect of IL-17A in a laser-induced CNV model and reveal a novel regulatory role of IL-17A-producing γδ T cells in the ocular microenvironment in wet AMD.

The effect of genetic variation and mRNA expression of interleukin-17A gene on susceptibility to asthma.

Analyzing the genetic variation and mRNA expression of interleukin-17A (IL-17A) gene and its impact on asthma susceptibility was the purpose of this study. 120 asthma patients were selected as the asthma group, and another 120 healthy individuals who underwent physical examination were selected as the health group; Compare the cytokine levels and mRNA expression of IL-17A between two groups, as well as the clinical indicator total immunoglobulin E (TIgE) levels; The genotype and allele distribution frequency of IL-17A Single-nucleotide polymorphism locus rs2275913 and rs8193036 were compared between the two groups; Compare the serum IL-17A and TIgE levels of different genotypes at rs2275913 and rs8193036 loci; and logistic regression was used to evaluate the impact of IL-17A on asthma susceptibility. The serum levels of IL-17A, TIgE, and IL-17AmRNA expression in the asthma group were higher than those in the healthy group (P<0.05). There were three genotypes of AA, AG and GG at rs2275913 locus, and the frequency distribution between the two groups was significant (P<0.05), and the frequency of A Allele frequency in asthma group was higher than that in healthy group (P<0.05). There are three genotypes of CC, CT, and TT at the rs8193036 locus, and there was no significant difference in the frequency distribution between the two groups (P>0.05). There is no difference in the frequency distribution of alleles C and T between the two groups (P>0.05). The levels of IL-17A and TIgE in the rs2275913AA genotype were higher than those in the AG and GG genotypes (P<0.05); There was no difference in IL-17A and TIgE levels among different genotypes of rs8193036 (P>0.05). The rs2275913 polymorphism was associated with asthma susceptibility and is an independent risk parameter for asthma susceptibility. Upregulation of serum IL-17A and TIgE, as well as overexpression of IL-17A mRNA, were closely related to asthma susceptibility in asthma patients. The rs2275913 polymorphism had a significant role in increasing the risk of asthma, and variant allele A may be a susceptibility factor for increasing asthma risk.

Expression of interleukin-17A in serum of children with intravenous immunoglobulin-resistant Kawasaki disease and its clinical significance

To study the expression of interleukin-17A (IL-17A) in the serum of children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and its clinical significance. A total of 143 children with KD who were hospitalized in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2021 to June 2022 were enrolled in this prospective study, among whom 115 had IVIG-sensitive KD and 28 had IVIG-resistant KD. After matching for sex and age, 110 children with acute respiratory infectious diseases (fever time ≥5 days but without KD) were enrolled as the control group. The enzyme-linked immunosorbent assay was used to measure the serum level of IL-17A. The levels of white blood cell count (WBC), neutrophil count (NE), platelet count, erythrocyte sedimentation rate, and C-reactive protein (CRP) were measured. The receiver operating characteristic curve was plotted to analyze the value of WBC, NE, CRP, and IL-17A in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis was used to evaluate the predictive factors for resistance to IVIG in children with KD. Before IVIG treatment, the KD group had a significantly higher serum level of IL-17A than the control group (P<0.05), and the children with IVIG-resistant KD had a significantly higher serum level of IL-17A than those with IVIG-sensitive KD (P<0.05). The receiver operating characteristic curve analysis showed that WBC, NE, CRP, and IL-17A had an area under the curve of 0.718, 0.741, 0.627, and 0.840, respectively, in the prediction of IVIG-resistant KD. With serum IL-17A ≥44.06 pg/mL as the cut-off value, IL-17A had a sensitivity of 84% and a specificity of 81% in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis showed that a high serum level of IL-17A was a predictive factor for resistance to IVIG in children with KD (OR=1.161, P=0.001). Serum IL-17A levels are elevated in children with IVIG-resistant KD, and serum IL-17A level (≥44.06 pg/mL) may have a predictive value for resistance to IVIG in children with KD.

Immunogenetic Role of IL17A Polymorphism in the Pathogenesis of Recurrent Miscarriage.

Interleukin-17A (IL17A) is a proinflammatory cytokine and is assumed to play an important role in fetal rejection. In order to evaluate the potential role of IL17A polymorphism in the pathogenesis of recurrent miscarriage (RM), serum IL17A levels were estimated by ELISA. Single-nucleotide polymorphism was assessed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) using gene-specific primers and the EcoNI restriction enzyme. Serum IL17A levels were nonsignificantly (p &gt; 0.5) low in RM patients compared with the control group. IL17A gene amplification by PCR yielded the undigested product of 815 bp, and its digestion with EcoNI enzyme produced 815, 529, 286, and 270 bp fragments for the GG genotype; 529, 286, and 270 bp fragments for the GA genotype; and 529 and 286 bp fragments for the AA genotype. The genotype frequency between the RM and control groups exhibited a significant difference (p = 0.001), whereas no significant difference was observed between allele frequencies in the two groups (p = 0.0954). These data suggest that the IL17A gene polymorphism exhibits no significant effect on IL17A gene expression. However, it significantly decreases and increases RM risk in the homozygous and recessive models, suggesting its potential pregnancy-protecting and -harming roles in the AA and GA + GG genotypes, respectively.

Self-education Program for Osteoarthritis Reduces Sodium Intake, Knee Joint pain, and Serum Interleukin-17A level in Osteoarthritis Patients

Objectives: As it has been known that sodium may aggravate joint inflammation throuh IL-17A pathway and it can cause joint pain, the purpose of this study was to determine the effect of the Self Education Programs for Osteoarthritis (SEPO) intervention on sodium intake, knee join pain and IL-17A level in patients with knee osteoarthritis.&#x0D; Methods: This multicenter study was conducted in orthopedic and internal medicine outpatient wards in three hospitals. This research has received ethical approval. Patients were recruited based on accidental sampling, who met the inclusion criteria. SEPO intervention was carried out for 30 days, followed by provision of leaflets, posters, and handbook about osteoarthritis, daily WhatsApp education chat and/or video. Patients’ demographic, knee joint pain, and sodium intake data was collected during interview, using the Semi Quantitative Food Frequency Questionnaire (SQ_FFQ), and WOMAC (Western Ontario McMaster Osteoarthritis Index) whereas serum IL-17A was determined by using ELISA. The effect of SEPO was analyzed statistically using Mann Whitney tests (p&lt; 0.05).&#x0D; Results: Total subjects recruited were 80, namely 30 patients in control group and 50 patients in treatment group. Majority of patients were female (74, 92.5%), age 56-65 yo (32, 40%), obese (54, 67.5%) and senior high school (23, 46%). Statistical results showed that following SEPO intervention daily sodium intake was lower (1289.45±457.98 mg) compared to the control group (2143.94±744.75 mg), p= 0.04. WOMAC score of control group (28±12.41) higher than treatment group (23.88±13.61), p=0.02. Serum IL-17A levels were also lower in the treatment group (3.974±1.06 pg/mL) than the control group (5.542±1.99 pg/ml), p=0.01.&#x0D; Discussion: Education as a non-pharmacological therapy is needed to reduce disease progression. Education is provided according to the patient's needs. Educational models can be offline (face to face) or online (digital). SEPO intervention in patients with knee osteoarthritis can reduce sodium intake, knee joint pain, and may impact on reduction of serum IL-17A.&#x0D;

High Serum IL-17A Is Associated with Bone Destruction in Newly Diagnosed Multiple Myeloma Patients

Background Multiple myeloma (MM) is a malignant proliferative disease of the blood system, characterized by the abnormal growth of clonal plasma cells in the bone marrow. The bone marrow microenvironment (BMM) is highly critical in the pathological process of MM. Many studies have shown that serum Interleukin-17A (IL-17A) plays a key role in various infectious diseases, autoimmune diseases, and cancers. However, more clinical researches need to be done to further proof the influence of serum IL-17A level on multiple myeloma patients. Methods Among a total of 357 participants in our institution's MM cohort, 175 were eligible for the retrospective study. Multivariate regression models adjusted by potential confounding factors, the violin plots, the generalized additive model and smooth curve fittings, receiver operating characteristic (ROC) curve and K-M curve analysis were applied to the research. Results A total of 175 patients with newly diagnosed MM were enrolled in this study. The multivariate linear regression analysis showed that serum IL-17A level in MM patients correlated with the degree of bone lesions and fracture incidence (Fully adjusted model, Pbone lesion<0.0001, Pfracture<0.0001). Violin plot showed that MM patients with higher serum IL-17A level had more sever bone lesions and higher fracture incidence than that with lower serum IL-17A level. 171 patients were included in the study of the relationship between serum IL-17A and best overall effect (BOE). We found that serum IL-17A level were independently related to the best inductive therapeutic efficacy (Fully adjusted model, P =0.037), and the relationship was especially obvious in the light chain group (Fully adjusted model, P=0.009) and IgA (Fully adjusted model, P=0.0456). It could be deduced from the smooth curve that the higher the serum IL-17A level, the worse the BOE (P=0.0163). The ROC prediction curve suggested that serum IL-17A could predict the BOE to a certain extent (AUC=0.717, P=0.0327). A total of 148 MM patients were observed in the longitudinal study of relationship between serum IL-17A and PFS/OS. The K-M curve analysis indicated that serum IL-17A levels in MM patients were not significantly correlated with PFS and OS. However, in the light chain subgroup, MM patients with high serum IL-17A had worse PFS (P=0.015) and OS (P=0.0076) compared to that with low serum IL-17A. In IgA type subgroup, the higher IL-17A level was related to worse OS (P=0.0061). Conclusion This retrospective study found that higher levels of serum IL-17A was independently correlated with higher severity of bone disease and fractures incidence in newly diagnosed MM patients. High serum IL-17A level was related with poor best overall efficacy in light chain type. High serum IL-17A was also associated with poor PFS and OS in light chain type, and OS in IgA type subgroup.

Gancao Fuzi decoction regulates the Th17/Treg cell imbalance in rheumatoid arthritis by targeting Foxp3 via miR-34a

Ethnopharmacological relevanceDuring the Eastern Han Dynasty, Zhang Zhongjing first recorded the Gancao Fuzi decoction (GCFZD) formula in the “Synopsis of the Golden Chamber”, which is reportedly an effective and safe treatment for rheumatoid arthritis (RA). However, the mechanism underlying the observed improvement in the T helper 17 (Th17)/regulatory T (Treg) cell imbalance in RA obtained with GCFZD has not been reported. Aim of the studyThis study aimed to demonstrate whether GCFZD ameliorated RA by modulating the Th17/Treg imbalance in RA mice. Materials and methodsCollagen was used to induce a model of collagen-induced arthritis (CIA) in mice. GCFZD was administered by gavage, and the arthritis index score, imaging and histopathological changes of the ankle joints, and the levels of the immunoglobulin G (IgG) class antibodies and proinflammatory factors in serum were determined. In addition, the frequencies of Th17 and Treg cells, the levels of relevant transcription factors and functional factors and the miR-34a gene in the spleen and the levels of interleukin-17A (IL-17A) and IL-10 in serum were determined. ResultsGCFZD significantly reduced the arthritis score, improved joint swelling and bone damage, reduced the pathological score, and decreased the serum levels of IgG class antibody (IgG and IgG2a) and proinflammatory factor [tumour necrosis factor-alpha (TNF-α), IL-1β and IL-6]. Moreover, the Th17-cell proportion, the expression level of the Th17-specific transcription factor retinoic acid-related orphan receptor γt (RORγt) and functional factor IL-17A in the spleen, and the serum IL-17A level were decreased, whereas the Treg cell proportion, expression levels of the Treg-specific transcription factor forkhead box P3 (Foxp3) and functional factor IL-10 in the spleen, and the serum IL-10 level were increased. Furthermore, GCFZD inhibited miR-34a gene expression while promoting Foxp3 protein expression. ConclusionsThe findings of this study demonstrate the therapeutic effect of GCFZD on mice with CIA, and the mechanism is related to an improvement in the Th17/Treg cell imbalance by targeting Foxp3 via miR-34a.

The Effects of Combuxil and Leizumab on Retinal Function and Serum Interleukin-17A in Premature Infants with Retinopathy.

Objective To investigate the effects of Compaximab and raizumab on retinal function and serum interleukin-17A level in retinopathy of prematurity. Methods Sixty cases of retinopathy of prematurity treated in our hospital from February 2019 to April 2021 were selected. The patients were randomly divided into control group (n = 30) and research group (n = 30). The control group was treated with Compaq and the research group was treated with razumab. The curative effect, retinal function, incidence of complications, intraocular pressure at different time, and the level of serum interleukin-17A were compared. Results Compared with the two groups, the curative effect of the research group 93.33% (28/30) was greater than that of the control group 66.67% (20/30), and the difference was statistically significant (P < 0.05). Compared with the incidence of complications, the incidence of corneal opacity, lens opacity, preretinal and vitreous hemorrhage, endophthalmitis, and traction retinal detachment in the research group was greatly lower, and the difference was statistically significant (P < 0.05). Following the therapy, the IOP of the two groups decreased at different times. The IOP of 1 min, 10 min, and 30 min in the research group was obviously lower, and the difference was statistically significant (P < 0.05). Following treatments, the levels of serum IL-17A were decreased. Compared with the control group, the level of serum IL-17A in the research group was greatly downregulated, and the difference was statistically significant (P < 0.05). Conclusion Intravitreal injection of razumab is an effective treatment for retinopathy of prematurity, which can effectively improve the retinal function of infants. The level of serum interleukin-17A can be reduced and intraocular pressure can be regulated, which is safe and effective.

High serum IL-17A is associated with bone destruction in newly diagnosed multiple myeloma patients.

BackgroundMultiple myeloma (MM) is a malignant proliferative disease of the blood system, characterized by the abnormal growth of clonal plasma cells in the bone marrow. The bone marrow microenvironment (BMM) is highly critical in the pathological process of MM. Many studies have shown that serum interleukin-17A (IL-17A) plays a key role in various infectious diseases, autoimmune diseases, and cancers. However, more clinical studies need to be performed to further prove the influence of serum IL-17A levels on multiple myeloma patients.MethodsAmong a total of 357 participants in our institution’s MM cohort, 175 were eligible for the retrospective study. Multivariate regression models adjusted by potential confounding factors, the violin plots, the generalized additive model and smooth curve fittings, receiver operating characteristic (ROC) curve, and Kaplan–Meier (K-M) curve analysis were applied to the research.ResultsA total of 175 patients with newly diagnosed MM were enrolled in this study. The multivariate linear regression analysis showed that serum IL-17A level in MM patients correlated with the degree of bone lesions and fracture incidence (fully adjusted model, pbone lesion < 0.0001, pfracture < 0.0001). The violin plot showed that MM patients with higher serum IL-17A levels had more severe bone lesions and higher fracture incidence than those with lower serum IL-17A levels. A total of 171 patients were included in the study of the relationship between serum IL-17A and best overall effect (BOE). We found that serum IL-17A levels were independently related to the best inductive therapeutic efficacy (fully adjusted model, p = 0.037), and the relationship was especially obvious in the light chain group (fully adjusted model, p = 0.009) and IgA group (fully adjusted model, p = 0.0456). It could be deduced from the smooth curve that the higher the serum IL-17A level, the worse the BOE (p = 0.0163). The ROC prediction curve suggested that serum IL-17A could predict the BOE to a certain extent (area under the curve (AUC) = 0.717, p = 0.0327). A total of 148 MM patients were observed in the longitudinal study of the relationship between serum IL-17A and progression-free survival/overall survival (PFS/OS). The K-M curve analysis indicated that serum IL-17A levels in MM patients were not significantly correlated with PFS and OS. However, in the light chain subgroup, MM patients with high serum IL-17A had worse PFS (p = 0.015) and OS (p = 0.0076) compared to those with low serum IL-17A. In the IgA type subgroup, the higher IL-17A level was related to worse OS (p = 0.0061).ConclusionThis retrospective study found that higher levels of serum IL-17A were independently correlated with higher severity of bone disease and fracture incidence in newly diagnosed MM patients. High serum IL-17A level was related to poor best overall efficacy in the light chain type. High serum IL-17A was also associated with poor PFS and OS in the light chain type and OS in the IgA type subgroup.

IL-17A drives cognitive aging probably via inducing neuroinflammation and theta oscillation disruption in the hippocampus

Cognitive aging is a major risk factor for neurodegenerative diseases and has a great impact on the living quality of older individuals. However, the precise mechanisms underlying cognitive aging remain elusive. Accumulating evidence has demonstrated that interleukin 17A (IL-17A) is responsible for cognitive decline in the process of various neurological diseases. Thus, we conducted this study aiming to investigate the role of IL-17A in cognitive aging. In the present study, 31 aging (65–85 years) and 25 young (18–35 years) patients scheduled for elective removal of internal fixation surgery with spinal anesthesia were included for measurements of preoperative cognitive function, serum and cerebrospinal fluid (CSF) levels of IL-17A. For animal study, RNAseq and Kyoto Encyclopedia of Genes and Genomes pathways were used to identify differentially expressed genes between young and aging mice. For the treatment groups, young (2–3 months) and aging (16–18 months) mice received intraperitoneally with IL-17A and anti-IL-17A antibody, respectively. Twenty-four hours later, neurocognitive behavioral tests were conducted. Our results suggested that differentially expressed genes between young and aging mice were mainly enriched in IL-17 pathways. Serum and CSF levels of IL-17A increased significantly in aging patients and were negatively correlated with mini-mental state examination scores. Both young mice receiving IL-17A and aging mice showed impaired memory, increased blood-brain barrier permeability, overactivated microglia and increased inflammatory mediators in the hippocampus. Additionally, aging mice showed a significantly decreased θ power in the task-related neural oscillations. Notably, intraperitoneal injection of anti-IL-17A antibody alleviated increased blood-brain barrier permeability, microglial activation, neuroinflammation, θ oscillation disruption and cognitive decline of aging mice. In conclusion, our study demonstrated that IL-17A may be an initiating factor of cognitive aging.

AB0082 ANTI-INFLAMMATORY EFFECTS OF TOTAL SAPONINS OF PANAX JAPONICUS ON RHEUMATOID ARTHRITIS

BackgroundRheumatoid arthritis (RA) is a common autoimmune disease with inflammation[1]. Total saponins of Panax japonicus (TSPJs) are effective components extracted from Panax japonicus[2]. They are known to exhibit anti-inflammatory and immunosuppressoive properties, but their effect of anti-inflammation in collagen-induced arthritis (CIA) remains unclear.ObjectivesTo investigate the anti-inflammatory targets of TSPJ predicted by bioinformatics and the verification in CIA mice.MethodsThe targets of RA are obtained in the GeneCards database. we used Cytoscape 3.7.2 software to construct a protein-protein interactions (PPI) network and obtain the hub genes. There are four effective components of TSPJ: Araloside A, chikusetsusaponin IVa, ginsenoside Rg2, and ginsenoside Ro. Through molecular docking between the screened hub genes and the four effective components of TSPJ, the possibility of TSPJ treating CIA mice can be predicted. The collagen II (CII) and complete Freund’s adjuvant (CFA) were used to induce the CIA model. After establishing the model, 32 DBA1/J mice were divided into C group (n=8), M group (n=8), L group(n=8), and H group(n=8). The L and H groups were gavaged with TSPJ at 30 mg/kg or 150 mg/kg, and the C and M groups were gavaged with normal saline. The thickness of the hind paw, number of swollen joints, and arthritis index were evaluated. After 11 days of treatment, all the mice were sacrificed after anesthesia. Sera were collected to centrifuge tubes and the levels of inflammatory factor were determined by the ELISA kit following the instruction.ResultsA gene list that enriches 263 genes was obtained by searching RA from the GeneCards database. The hub genes of the top 3 obtained from Cytoscape 3.7.2 software were tumor necrosis factor (TNF), interleukin-1β (IL-1β), and interleukin-6 (IL-6). In addition, interleukin-17A (IL-17A), a classical inflammatory index in the top 10, was selected and included in the predicted target. The results of molecular docking between the predicted target and the components of TSPJ showed that the combined pose has good stability. The numerical value of hind paw thickness, swollen joint counts, and arthritis index in the intervention groups were lower than those in the M group, suggesting TSPJ played a critical role in improving pathological changes. Compared to those of the C group, the serum levels of TNF-α, IL-1β, IL-6, and IL-17A were increased in the M group. Compared to those of the M group, the levels of TNF-α, IL-1β, IL-6, and IL-17A in the L and H groups were decreased. Compared to those of the L group, the levels of TNF-α, IL-1β, IL-6, and IL-17A in the H group were decreased. The results suggested that TSPJ may decrease the levels of TNF-α, IL-1β, IL-6, and IL-17A in CIA mice. These results suggest that TSPJ may inhibit the inflammatory effects of CIA mice.ConclusionCurrent study demonstrated a novel inhibitory effect of TSPJ on inflammation in CIA mice, and TSPJ can act on the targets predicted by bioinformatics of CIA mice, suggesting the potential of TSPJ as a therapeutic agent for RA and providing new ideas for the clinical treatment of RA.

Interleukine-17 Modulates Neurogenesis and Behavior Following Exposure to Trauma in Mice.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder accompanied by deficits in cognitive and social skills. Adult hippocampal neurogenesis is a lifelong phenomenon, with new neurons being formed in the granular cell layer of the dentate gyrus. Impaired neurogenesis is associated with multiple behavioral disorders including Alzheimer’s disease and schizophrenia. PTSD patients often present hippocampal atrophy and animal models clearly present impaired neurogenesis. Previous studies on PTSD patients demonstrated elevated levels of Th17 cells and plasma levels of the pro-inflammatory cytokine interleukin-17A (IL-17A). Since IL-17A can impair neurogenesis in mice, we thus hypothesized that decreasing the serum levels of IL-17A will increase hippocampal neurogenesis and alleviate symptoms in a murine model of PTSD. Surprisingly, our results showed that attempting to neutralize IL-17A with an antibody resulted in increased serum levels of IL-17A, while targeting IL-23, the upstream regulator of IL-17, did lower the levels of IL-17A in trauma-exposed mice. As expected, increased levels of serum IL-17A (in anti-IL-17A treated mice) resulted in impaired neurogenesis, reflected by reduced number of proliferating Ki67+ neural progenitors and newly formed DCX+ neurons, which was correlated with increased expression of Hes1. Nevertheless, increased maturation was noted by the expression of Slit2 and Ache. In contrast, treatment with anti-IL-23 indeed resulted in increased neurogenesis. Behaviorally, both treatments did not affect trauma-related freezing behavior but did affect trauma-related social deficits. Unexpectedly, increased levels of serum IL-17A (in anti-IL-17A treated mice) prevented social deficits in trauma-exposed mice while anti-IL-23 exacerbated these deficits. We thus conclude that IL-17 is involved in regulating neurogenesis following exposure to stress but may be important in maintaining social behavior.

Interleukin17A: A Potential Target for Its Plausible Roles in the Pathogenesis of Idiopathic Epistaxis.

Introduction:It has been reported that inflammation may be a potential risk factor for the progression of epistaxis. Due to the major roles played by Th17 in the induction of inflammation, the present study aimed to assess the serum levels of Interleukin 17A (IL-17A) and IL-23, as the most important cytokines in the Th17 pathway, as well as IFN-, IL-4, and IL-10 serum levels, as regulatory cytokines for Th17 cells in patients with idiopathic epistaxis. Materials and Methods:The serum levels of IL-4, IL-10, IL-17A, IL-23, and IFN- were evaluated in 90 patients with idiopathic epistaxis and 90 healthy controls using enzyme-linked immunosorbent assay (ELISA) technique.Results:The obtained results pointed out that the serum levels of IL-17A and IL-10, but not IL-4 and IL-23, were significantly up-regulated, and IFN- serum levels were significantly down-regulated in patients with idiopathic epistaxis. Furthermore, female patients with epistaxis had higher IL-10 serum levels. Conclusions:As evidenced by the results of the present study, IL-17A is the main cytokine which participates in the pathogenesis of idiopathic epistaxis; moreover, in association with IL-10, it can be regarded as the suppressor of IFN- in patients.

Increased serum interleukin- 17A levels correlate with disease severity and poor prognostic factors in patients with alopecia areata.

Alopecia areata (AA) is a tissue-specific autoimmune disease characterized by non-scarring and rapid onset of hair loss. Interleukin (IL)-17A is mainly produced by T helper 17 (Th17) cells and may play a crucial role in the pathogenesis of various autoimmune diseases including AA. We conducted this research to measure serum level of IL-17A in patients with AA and investigated its relationship with the clinical manifestations in patients with AA. We assessed 36 patients with AA and 20 healthy control subjects. Demographic information and clinical characteristics were determined by physical examination and via the review of medical history. Serum IL-17A was measured by using enzyme-linked immunosorbent assay. Serum IL-17A concentration was significantly higher in patients with AA than in the control group (P=0.004). The AA patients with severe presentation, personal atopy, nail abnormalities, or active phase had significantly higher serum IL- 17A levels compared to others without these signs. Increased serum IL-17A levels in patients with AA correlate with severity and indicate an active disease state. These findings suggest that IL-17A may play an important role in determining the pathogenesis of AA and may serve as a valuable clinical biomarker of this disease.

Cross-Sectional Analysis of the Involvement of Interleukin-17A in Diabetic Retinopathy in Elderly Individuals with Type 2 Diabetes Mellitus.

BackgroundTo investigate the correlation between serum interleukin-17A (IL-17A) levels and diabetic retinopathy (DR) in elderly individuals with type 2 diabetes mellitus (T2DM).MethodsThe study included 194 elderly patients (94 males and 100 females) with T2DM. Digital retinal photography as well as fundus fluorescein angiography was employed to distinguish between nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). In addition, multiple logistic regression analysis was conducted to determine the correlation between serum IL-17A levels and DR status.ResultsThe average age of the study cohort was 69.14 ± 6.33 years, of which 52.08% were male. The study participants with the highest IL-17A (Q4) levels had higher TC, DBP, and low-density lipoprotein cholesterol (LDL-C) values than those the other groups. Analysis using unadjusted and adjusted linear regression revealed that the effect size of 1.09 for DR in the unadjusted model indicates that IL-17A is associated with an increase of 1.09 in DR (mmol/L) (β 1.09, 95% confidence interval (CI) 1.03, 1.16). Using the minimum-adjusted model (the model 2), as IL-17A increased, DR was higher by 1.11 (β 1.11, 95% CI 1.04, 1.18). With the fully adjusted model (the model 3), for each additional IL-17A increase, DR was higher by 1.15 (β 1.15, 95% CI 1.06, 1.24).ConclusionSerum IL-17A levels are apparently positively correlated to DR in Chinese elderly individuals with T2DM.

Interleukin-17A serum levels in young patients with atopic dermatitis and food allergy

Interleukin-17A serum levels in young patients with atopic dermatitis and food allergy