Higher Levels Of interleukin-17A Research Articles

Association of inflammatory biomarkers and disease activity with subclinical myocardial dysfunction in psoriatic arthritis

We examined the role of adipokines and pro-inflammatory cytokines in psoriatic arthritis-associated subclinical myocardial dysfunction, and the relationship between these variables and psoriatic arthritis (PsA) disease activity. Fifty-five PsA patients without cardiovascular risk factors and 25 controls underwent standard and speckle tracking echocardiography with global longitudinal strain (GLS) calculated. Standard anthropometric data and Disease Activity in Psoriatic arthritis (DAPSA) scores were recorded, with low disease activity defined as DAPSA ≤ 14 and moderate and high disease activity DAPSA > 14. Standard biochemical tests, adiponectin, resistin, leptin, tumor necrosis factor (TNF) alfa, interleukin 17 A (IL-17A), B lymphocyte chemoattractant (BLC), and monokine induced by intereferon gamma (MIG) were analyzed. Median age was 53.0 (46.0–61.0), median PsA duration 6.0 (4.0–13.0) years and median DAPSA score 25.5 (13.0–41.5). Lower GLS, tricuspid annular plane systolic excursion (TAPSE) and left ventricular ejection fraction (LVEF) were found in moderate and high PsA disease activity compared to low PsA disease activity and controls. PsA patients with GLS < 20 had higher body mass index (BMI), DAPSA score and uric acid levels, and lower adiponectin levels. Although patients with GLS < 20 had higher IL-17A levels, it was not statistically significant (P = 0.056). However, when we included healthy controls and analyzed differences based on a GLS cut-off of 20% in the entire population, the difference in IL-17A became statistically significant, 0.17 pg/mL (0.06–0.32) vs. 0.43 pg/mL (0.23–0.65), P = 0.017. The association between DAPSA score and GLS and IL-17 remained significant in multivariate analysis. Moreover, the association between GLS and IL-17 and adiponectin was significant after adjustment for age and BMI. Patients with moderate and high PsA disease activity have reduced myocardial function, lower adiponectin, and higher IL-17A levels.

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.

Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy.

Interleukin 17A (IL-17A) was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications. However, the role of IL-17A in diabetic encephalopathy remains poorly understood. In this study, we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a-/- mice with spontaneously diabetic Ins2Akita (Akita) mice. Blood glucose levels and body weights were monitored from 2-32 weeks of age. When mice were 32 weeks of age, behavioral tests were performed, including a novel object recognition test for assessing short-term memory and learning and a Morris water maze test for evaluating hippocampus-dependent spatial learning and memory. IL-17A levels in the serum, cerebrospinal fluid, and hippocampus were detected with enzyme-linked immunosorbent assays and real-time quantitative polymerase chain reaction. Moreover, proteins related to cognitive dysfunction (amyloid precursor protein, β-amyloid cleavage enzyme 1, p-tau, and tau), apoptosis (caspase-3 and -9), inflammation (inducible nitric oxide synthase and cyclooxygenase 2), and occludin were detected by western blot assays. Pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interferon-γ in serum and hippocampal tissues were measured by enzyme-linked immunosorbent assays. Microglial activation and hippocampal neuronal apoptosis were detected by immunofluorescent staining. Compared with that in wild-type mice, mice with diabetic encephalopathy had higher IL-17A levels in the serum, cerebrospinal fluid, and hippocampus; downregulation of occludin expression; lower cognitive ability; greater loss of hippocampal neurons; increased microglial activation; and higher expression of inflammatory factors in the serum and hippocampus. IL-17A knockout attenuated the abovementioned changes in mice with diabetic encephalopathy. These findings suggest that IL-17A participates in the pathological process of diabetic encephalopathy. Furthermore, IL-17A deficiency reduces diabetic encephalopathy-mediated neuroinflammation and cognitive defects. These results highlight a role for IL-17A as a mediator of diabetic encephalopathy and potential target for the treatment of cognitive impairment induced by diabetic encephalopathy.

Investigation of IL-17A Serum Levels in Patients with Nonmelanoma Skin Cancer.

Background Role of interleukin 17A (IL-17A) in carcinogenesis and cancer growth is controversial. Although some researches support its antitumor activity, some others suggest that it promotes the growth and development of different types of cancer including skin cancer by activation of STAT3. Although the function of the cytokines such as IL-17A has been extensively studied in various types of cancer, nonmelanoma skin cancer (NMSC) has not received much attention. Therefore, the present study was aimed to investigate the serum levels of IL-17A in NMSC patients. Methods This cross-sectional study was performed on 60 patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) as well as 57 age-sex matched healthy individuals as control group. Measurement of IL-17A serum levels in both case and control groups was performed by a commercially reliable sandwich enzyme-linked immunosorbent assay (ELISA) kit. Results In this study, we observed that IL-17A serum levels in NMSC patients were significantly higher than the control group (P < 0.001). Also, both BCC and SCC patients had higher levels of IL-17A in their sera in comparison to the controls (P=0.001 and P < 0.001, respectively). However, there was no significant difference between SCC and BCC patients regarding serum levels of IL-17A. Conclusion According to our results, it can be concluded that IL-17A may play a role in inducing the growth and progression of NMSC and it can be used as a therapeutic target in these patients in future.

Baseline and early functional immune response is associated with subsequent clinical outcomes of PD-1 inhibition therapy in metastatic melanoma patients

BackgroundDespite significant progress with antiprogrammed cell death protein 1 (PD-1) therapy, a substantial fraction of metastatic melanoma patients show upfront therapy resistance. Biomarkers for outcome are missing and the association...

Interleukin-17A Promotes Lung Tumor Progression through Neutrophil Attraction to Tumor Sites and Mediating Resistance to PD-1 Blockade

IntroductionProinflammatory cytokine interleukin-17A (IL-17A) is overexpressed in a subset of patients with lung cancer. We hypothesized that IL-17A promotes a protumorigenic inflammatory phenotype and inhibits antitumor immune responses. MethodsWe generated bitransgenic mice expressing a conditional IL-17A allele along with conditional KrasG12D and performed immune phenotyping of mouse lungs, a survival analysis, and treatment studies with antibodies either blocking programmed cell death 1 (PD-1) or IL-6 or depleting neutrophils. To support the preclinical findings, we analyzed human gene expression data sets and immune profiled patient lung tumors. ResultsTumors in IL-17:KrasG12D mice grew more rapidly, resulting in a significantly shorter survival as compared with that of KrasG12D mice. IL-6, granulocyte colony-stimulating factor (G-CSF), milk fat globule-EGF factor 8 protein, and C-X-C motif chemokine ligand 1 were increased in the lungs of IL17:Kras mice. Time course analysis revealed that levels of tumor-associated neutrophils were significantly increased, and lymphocyte recruitment was significantly reduced in IL17:KrasG12D mice as compared with in KrasG12D mice. In therapeutic studies PD-1 blockade was not effective in treating IL-17:KrasG12D tumors. In contrast, blocking IL-6 or depleting neutrophils with an anti–Ly-6G antibody in the IL17:KrasG12D tumors resulted in a clinical response associated with T-cell activation. In tumors from patients with lung cancer with KRAS mutation we found a correlation between higher levels of IL-17A and colony- stimulating factor 3 and a significant correlation among high neutrophil and lower T-cell numbers. ConclusionsHere we have shown that an increase in a single cytokine, IL-17A, without additional mutations can promote lung cancer growth by promoting inflammation, which contributes to resistance to PD-1 blockade and sensitizes tumors to cytokine and neutrophil depletion.

Is Interleukin‐17 Involved in the Interaction Between Polycystic Ovary Syndrome and Gingival Inflammation?

Polycystic ovarian syndrome (PCOS) is a hormonal disorder of females of reproductive age that impacts their oral and systemic health. The aim of this study is to evaluate interleukin-17A (IL-17A), IL-17F, IL-17A/F, and IL-17E (IL-25) levels in gingival crevicular fluid (GCF), saliva, and serum of non-obese females with PCOS and with either a clinically healthy periodontium or gingivitis. Thirty-one females with PCOS, 30 females with PCOS and gingivitis, and 12 systemically and periodontally healthy females participated in the study. Clinical periodontal measurements, body mass index, and Ferriman-Gallwey score (FGS) (a measure of hirsutism in females) were recorded. Circulating levels of sex hormones, cortisol, and insulin were also determined. Levels of IL-17 cytokines were measured by enzyme-linked immunosorbent assay. The general linear model multivariate analysis, adjusting for age or plaque index, showed that the two groups with PCOS had higher concentrations of IL-17A, IL-17F, and IL-17A/F in serum and higher levels of IL-17A and IL-17F in GCF and saliva but lower serum IL-17E than systemically healthy females. Levels of IL-17E were lowest in females with PCOS and gingivitis who also had the highest FGS. Serum IL-17A and IL-17F levels correlated positively with FGS and periodontal probing depth (all ρ >0.33; P <0.005). Serum IL-17E showed the reverse relationship and also correlated negatively with IL-17A (ρ >-0.28; P <0.05). IL-17 levels are altered in non-obese females with PCOS and may influence gingival inflammation. Additional studies are warranted to clarify the relationship between PCOS and gingivitis.