Role of gene polymorphisms/haplotypes and serum levels of interleukin-17A in susceptibility to viral myocarditis.

Interleukin-17A (IL-17A) has been implicated in the pathogenesis of viral myocarditis (VMC). However, the role of IL-17A polymorphisms in susceptibility to VMC has not been reported to date. The aim of this study was to explore the association between IL-17A variants as well as serum IL-17 levels with VMC. Three single-nucleotide polymorphisms (SNPs) (rs2275913, rs3819025, and rs3748067) were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method in 236 VMC patients and 259 controls from China. Serum IL-17A levels were measured by enzyme-linked immunosorbent assay kits. Multivariable logistic regression analysis that the rs2275913 AA genotype and the haplotype -197A/+45G/+1249G (AGG) were associated with an increased risk of VMC (all P < 0.05). Consistent with these findings, the rs2275913 AA genotype was linked to higher serum IL-17A compared to GG/AG genotype (all P < 0.001). We observed no associations between the other two SNPs and risk of VMC. Serum IL-17A levels were significantly higher in the VMC group than controls (P < 0.001) and gradually increased with the increase of New York Heart Association grade in VMC patients (P < 0.05). Spearman correlation test revealed that the serum IL-17A level was correlated with the cardiac damage and left ventricular systolic functions among VMC patients (all P < 0.05). Our study reveals that IL-17A expression may contribute to the development and severity of VMC. The SNP rs2275913 in the IL-17A gene might exert influence on susceptibility to VMC via linking with the serum IL-17A level.

The predictive value of serum IL-17A and IL-6 expression in postoperative recurrence in patients with intrauterine adhesion.

BACKGROUND: The recurrence rate of intrauterine adhesions (IUA) was high. At present, there are few studies on the relationship between proinflammatory factors IL-17A and IL-6 and IUA. The expression of serum IL-17A and IL-6 in IUA patients and their predictive value for postoperative recurrence were retrospectively analyzed. METHODS: A total of 90 IUA patients who underwent hysteroscopic adhesion lysis in our hospital from January 2020 to January 2023 were selected as the IUA group. Patients were divided into mild, moderate, and severe IUA groups. At the same time, 60 cases of secondary infertility patients with normal endometrium were selected as the control group. The clinical baseline characteristics and serum levels of IL-17A and IL-6 were compared between control group and IUA group. To analyze the correlation and predictive value of IL-17A and IL-6 expression levels with the recurrence rate of IUA patients. RESULTS: The preoperative levels of IL-17A and IL-6 in the IUA group were significantly higher than those in the control group. The higher the levels of inflammatory factors IL-17A and IL-6, the deeper the degree of IUA. Multivariate analysis showed that pregnancy, curettage history, IL-17A, and IL-6 levels were risk factors for IUA recurrence. In addition, the specificity and area under the curve of combining baseline data with postoperative serum IL-17A and IL-6 for predicting IUA were higher than those predicted separately. CONCLUSION: The expression levels of serum IL-17A and IL-6 can be used as a value index to evaluate postoperative recurrence in IUA patients.

Ιnterleukin-17A-Enriched Neutrophil Extracellular Traps Promote Immunofibrotic Aspects of Childhood Asthma Exacerbation.

Childhood asthma is a chronic inflammatory airway disorder that can drive tissue remodeling. Neutrophils are amongst the most prominent inflammatory cells contributing to disease manifestations and may exert a potent role in the progression of inflammation to fibrosis. However, their role in asthma exacerbation is still understudied. Here, we investigate the association between neutrophil extracellular traps (NETs) and lung fibroblasts in childhood asthma pathophysiology using serum samples from pediatric patients during asthma exacerbation. Cell-based assays and NETs/human fetal lung fibroblast co-cultures were deployed. Increased levels of NETs and interleukin (IL)-17A were detected in the sera of children during asthma exacerbation. The in vitro stimulation of control neutrophils using the sera from pediatric patients during asthma exacerbation resulted in IL-17A-enriched NET formation. The subsequent co-incubation of lung fibroblasts with in vitro-generated IL-17A-enriched NETs led fibroblasts to acquire a pre-fibrotic phenotype, as assessed via enhanced CCN2 expression, migratory/healing capacity, and collagen release. These data uncover the important pathogenic role of the NET/IL-17A axis in asthma exacerbation, linking lung inflammation to fibroblast dysfunction and fibrosis.

Interleukin-17 Links Inflammatory Cross-Talks Between Comorbid Psoriasis and Atherosclerosis.

Psoriasis is a chronic, systemic, immune-mediated inflammatory disorder that is associated with a significantly increased risk of cardiovascular disease (CVD). Studies have shown that psoriasis often coexists with atherosclerosis, a chronic inflammatory disease of large and medium-sized arteries, which is a major cause of CVD. Although the molecular mechanisms underlying this comorbidity are not fully understood, clinical studies have shown that when interleukin (IL)-17A inhibitors effectively improve psoriatic lesions, atherosclerotic symptoms are also ameliorated in patients with both psoriasis and atherosclerosis. Also, IL-17A levels are highly expressed in the psoriatic lesions and atherosclerotic plaques. These clinical observations implicit that IL-17A could be a crucial link for psoriasis and atherosclerosis and IL-17A-induced inflammatory responses are the major contribution to the pathogenesis of comorbid psoriasis and atherosclerosis. In this review, the current literature related to epidemiology, genetic predisposition, and inflammatory mechanisms of comorbidity of psoriasis and atherosclerosis is summarized. We focus on the immunopathological effects of IL-17A in both diseases. The goal of this review is to provide the theoretical base for future preventing or treating psoriasis patients with atherosclerosis comorbidity. The current evidence support the notion that treatments targeting IL-17 seem to be hold some promise to reduce cardiovascular risk in patients with psoriasis.

In vivo treatment with IL-17A attenuates hydatid cyst growth and liver fibrogenesis in an experimental model of echinococcosis.

We aimed to assess the effect of exogenous Interleukin (IL)-17A in experimental model of echinococcosis. Swiss mice were inoculated intra-peritoneally with viable protoscoleces (PSCs). Then, IL-17A was administered at 100, 125 or 150 pg/mL two weeks after cystic echinococcosis (CE) induction. Cyst development and hepatic damage were macroscopically and histologically analyzed. We observed that in vivo IL-17A treatment at 100, 125, and 150 pg/mL, reduced metacestode growth by 72.3%, 93.8%, and 96.9%, respectively. Interestingly an amelioration of liver architecture was noted at 125 pg/mL without toxic effect. In this context, we showed less fibrosis reaction and reduced expression of iNOS, TNF-α, NF-κb and CD68 in hepatic parenchyma of treated mice by 125 pg/mL of IL-17A. Collectively, our results indicate an antihydatic effect and immunoprotective properties of IL-17A and suggest its potential therapeutic value against Echinococcus granulosus infection.

Secukinumab efficacy and safety in indian patients with moderate-to-severe plaque psoriasis: Sub-analysis from FIXTURE, a randomized, placebo-controlled, phase 3 study.

TITLE: Secukinumab efficacy and safety in Indian patients with moderate-to-severe plaque psoriasis: sub-analysis from FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), a randomized, placebo-controlled, phase 3 study. BACKGROUND: Evidence has suggested Interleukin (IL)-17A to be an important effector cytokine in the pathogenesis of psoriasis. Here, we report results for an Indian sub-population from a multinational study FIXTURE, designed to assess the safety, tolerability, and long-term efficacy of fully human anti-IL-17A monoclonal antibody secukinumab in patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: In this double-dummy, placebo controlled, 52-weeks phase 3 study FIXTURE, 149 Indian patients were randomized 1:1:1:1 to receive secukinumab at a dose of 300 mg or 150 mg, etanercept, or placebo. The study objective was to show the superiority of secukinumab over placebo at week 12, vis-à-vis proportion of patients achieving a reduction of 75% or more from the baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (IGA mod 2011) (co-primary end points). RESULTS: At week 12, 61.0% and 55.9% patients in secukinumab 300 mg and 150 mg groups, respectively, achieved PASI 75 response compared to 20.0% in the etanercept and 7.1% in the placebo groups. Similarly, IGA mod 2011 0 or 1 response was achieved by 43.9% and 20.6% in patients in the secukinumab 300 mg and 150 mg group, respectively, vs. 13.3% in the etanercept and 2.4% in the placebo groups at week 12. Likewise, higher proportions of patients in secukinumab 300 mg (41.5%) and 150 mg (20.6%) group were PASI 90 responders at week 12 than those in the etanercept (10.0%) or placebo (0.0%) groups. The incidences of adverse events (AEs), during the induction period were similar in all the treatment groups. Overall secukinumab was well-tolerated at both doses in the Indian sub-population. CONCLUSION: The results from the Indian sub-population suggest that secukinumab is an efficacious and safe drug for use in moderate-to-severe chronic plaque psoriasis.

Immunization with Leishmania donovani protein disulfide isomerase DNA construct induces Th1 and Th17 dependent immune response and protection against experimental visceral leishmaniasis in Balb/c mice.

In the present study, the efficacy of Leishmania donovani protein disulfide isomerase (LdPDI) as a DNA vaccine was evaluated in BALB/C mice. Mice immunized with the LdPDI-DNA construct were found to be the most immuno-reactive, as the construct induced higher T-cell proliferation. The increased T-cell proliferation was associated with a substantial rise in Th1 and Th17+ CD4 cell response and triggered a higher proportion of CD8+ T cells for the release of interferon-gamma along with a reduced splenic parasite load on Days20 and 60 post challenge (PC). Furthermore, the vaccine construct triggered increased interferon (IFN)-γ, interleukin(IL)-17A, and IL-22 release accompanied by decreased extracellular signal-regulated kinases (ERK) 1/2 signaling and increased mitogen-activated protein kinase (MAPK) signaling coinciding with an increase in the amount of nitrite and reactive oxygen species (ROS)in vaccinating the splenocyts. We summarize from our data that the PDI-DNA construct of Leishmania donovani has the potential to elicit protective immunity through the pro-inflammatory cytokines of CD8+ and CD4+(Th1 and Th17) following an intervention in the downstream signaling event of ERK1/2 (probably through p38MAPK signaling). Therefore, the study suggests a new control against visceral leishmaniasis in the future.

The IL-17A/IL-17RA axis in pulmonary defence and immunopathology.

The interleukin (IL)-17A/IL-17 receptor A (IL-17RA) axis is emerging as a key player in host defence. Several studies have demonstrated that IL-17A-mediated responses play a critical role in both acute and chronic inflammation induced by infectious agents, environmental stimuli and genetic diseases in the airways. In this regard, it is becoming evident that IL-17A/IL-17RA signalling may have a protective and beneficial impact on health, but that it can also result in detrimental outcomes. On one hand, the IL-17A/IL-17RA axis can contribute to the elimination of noxious stimuli and to the resolution of acute inflammatory processes; on the other hand, it can exacerbate immunopathological responses, contributing to the development and progression of chronic respiratory illnesses. In addition, cellular and molecular signatures underlying IL-17A/IL-17RA signalling have been increasingly identified, although further studies are needed to clarify such complex responses. Here, we discuss the latest discoveries on the role of the IL-17A/IL-17RA axis in driving host pulmonary defence and immunopathology.