Serum interleukin-17A Research Articles

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.

Effects of Electroacupuncture Preconditioning at Baihui and Zusanli Acupoints on the Expression of Inflammatory Factors in Brain and Intestines of Rats with Cerebral Ischemia/Reperfusion

<sec><title>Objective</title> To observe the effects of electroacupuncture preconditioning on the expression of interleukin-17A（IL-17A）and IL-10 in the brain and intestine of rats with cerebral ischemia/reperfusion and to explore the brain-gut protective effect of electroacupuncture preconditioning. </sec><sec><title>Methods</title> A total of 36 male Sprague-Dawley rats were randomly divided into the sham group (S-con group), the model group (M-con group), and the electroacupuncture preconditioning group (EP group) ,with 12 cases in each group. The S-con group was operated according to the model of middle cerebral artery occlusion/reperfusion (MCAO/R) with no blocking of the cerebral blood flow and reperfusion. The M-con group was given the operation of MCAO/R model and the cerebral blood perfusion was restored after 120 minutes. The EP group was intervened by electroacupuncture preconditioning at Baihui (DU20) and Zusanli (ST36) acupoints for two weeks, and was given the operation of MCAO/R model after the last electroacupuncture intervention for 24 hours, the cerebral blood perfusion was restored after 120 minutes. Before surgery for one day, after reperfusion for 12 h and after reperfusion for 1,3,7 days, the grip tester was used to measure the forelimb grasping strength; after reperfusion for 7 days, ELISA methods was used to determine the content of IL-17A and IL-10 in serum, Western blot method was used to detect the expression of IL-17A and IL-10 protein in ischemic cortex and colon tissue, immunohistochemistry method was used to calculate the average optical density (AOD) value of IL-17A and IL-10 in ischemic cortex and colon tissue, and HE staining method was used to observe the pathological change of ischemic cortex. </sec><sec><title>Results</title> ① Forelimb grasping strength: compared with the S-con group, the forelimb grasping strength of rats in the M-con group after reperfusion for 12 h, 1 d, 3 d, 7 d was decreased significantly (<italic>P</italic><0.05); compared with the M-con group, the forelimb grasping strength of rats in the EP group was increased significantly (<italic>P</italic><0.05). ② Content of IL-17A and IL-10 in serum: after reperfusion for 7 days, compared with the S-con group, the content of serum IL-17A and IL-10 of rats in the M-con group were significantly increased (<italic>P</italic><0.05); compared with the M-con group, the content of serum IL-17A in the EP group were significantly decreased (<italic>P</italic><0.05), and IL-10 in the EP group were significantly increased (<italic>P</italic><0.05). ③ Expression of IL-17A and IL-10 protein: after reperfusion for 7 days, compared with the S-con group, the expression of IL-17A and IL-10 protein in ischemic cortex and colon tissue in the M-con group were significantly increased (<italic>P</italic><0.05); compared with the M-con group, the expression of IL-17A in the EP group was significantly decreased (<italic>P</italic><0.05), and the expression of IL-10 protein in the EP group was significantly increased (<italic>P</italic><0.05). ④ AOD value of IL-17A and IL-10: after reperfusion for 7 days, compared with the S-con group, the AOD value of IL-17A and IL-10 in ischemic cortex and colon tissue in the M-con group were significantly increased (<italic>P</italic><0.05); compared with the M-con group, the AOD value of IL-17A in the EP group was significantly decreased (<italic>P</italic><0.05), the AOD value of IL-10 in the EP group was significantly increased (<italic>P</italic><0.05). ⑤ Pathological change of ischemic cortex: after reperfusion for 7 days, compared with the M-con group, the pathological change of ischemic cortex in EP group was significantly decreased (<italic>P</italic><0.05). </sec><sec><title>Conclusion</title> Electroacupuncture preconditioning at Baihui and Zusanli acupoints can reduce the pathological damage degree of the ischemic cortex and intestinal-central inflammation, improve neurobehavioral function, which may be related to brain-gut protection. </sec>

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.

Закономірності зміни концентрацій ІЛ-17А, ІЛ-10 та ІЛ-2 у крові людей із гніздовою алопецією до та після лікування збагаченою тромбоцитами плазмою

Alopecia areata is a heterogeneous disease characterized by nonscarring hair loss. It affects 1-2% of the population of both genders and occurs in all age groups. According to the recent studies, helper T cells 1, helper T cells 2, helper T cells 17, and regulatory T cells may be the main possible initiators of alopecia areata. The purpose of the study was to determine the concentrations of serum interleukin-17A, interleukin-10 and interleukin-2 in patients with alopecia areata, and to study the relationship between their levels before and after treatment with platelet-rich plasma. Materials and methods. The study involved 37 patients with alopecia areata aged (35.7±8.9) years and 30 people of the control group aged (37.4±7.9) years. People with alopecia areata were injected with platelet-rich plasma. For this, immediately before administration, venous blood was taken from the patients from the cubital vein into a special tube for the preparation of platelet-rich plasma. Platelet-rich plasma was injected into the lesions at the rate of 0.2 ml/cm2 using an insulin syringe and a 30 G needle, once every 2 weeks for 16 weeks. The patients were examined before the treatment and in 3, 6 and 17 months. The concentrations of interleukin-17A, interleukin-2 and interleukin-10 were determined in blood serum before treatment and after 3, 6 and 17 months of observation by the Sandwich-ELISA method (enzyme-linked immunosorbent assay). Interleukin-17A, interleukin-2 and interleukin-10 in the blood serum in the control group were also determined. The software program SPSS 22.0 was used for the statistical analysis. The normality distribution was tested by Shapiro-Wilk’s method. Independent Student’s t-test for unpaired samples was used to compare mean values between groups. The p-value &lt; 0.05 was considered significant. Results and discussion. The results obtained in our study showed that the concentrations of the pro-inflammatory cytokines interleukin-17A and interleukin-2 were significantly higher in persons with alopecia areata before treatment. After 17 months of therapy with platelet-rich plasma, serum interleukin-17A and interleukin-2 levels approached the control level. Conclusion. There was no difference in the concentration of anti-inflammatory interleukin-10 between patients with alopecia areata and healthy people. In the course of treatment, the concentration of interleukin-10 increased after 3 and 17 months of therapy

Serum level of interleukin-17A in patients with alopecia areata and its relationship to age of patients and disease recurrence

Introduction Alopecia areata (AA) is a relatively common reversible patchy hair loss of the scalp. It is usually manifested as patchy areas of complete hair loss on the scalp and sometimes with or without other body parts that can progress to complete loss of all body hair. This disorder affects all age groups, with a higher incidence in children and adolescents. AA is an autoimmune disorder characterized by hair cycle dysfunction with peribulbar and perifollicular mononuclear cell infiltrates. Aim To estimate interleukin-17A (IL-17A) serum level in patients with AA as well as study its relationship with the age of the patients, severity, and recurrence of disease. Patients and method s The study was carried out in Outpatient Clinic of Dermatology, Venerology, and Andrology Department, Zagazig University Hospitals, on 45 patients with AA of both sexes. Results were compared with 45 healthy participants with matched age (5–50 years). Results The present study included two groups: patient group included 45 patients diagnosed clinically with AA and control group included 45 age-matched and sex-matched healthy individuals. Conclusion The significantly higher levels of serum IL-17A in patients with AA suggest a possible role of IL-17A as a proinflammatory cytokine in the pathogenesis of AA and that IL-17A level may be influenced by age and disease recurrence in patients with AA.

IL-17A and CCL2 in blood serum and circulating neutrophils in patients with ovarian tumors.

e17536 Background: During the ovarian carcinogenesis, circulating neutrophils (Nph) phenotype switches to the pro-tumor, with an increase in the Nph C-C motif ligand 2 (CCL2) expression. Proinflammatory interleukin-17A (IL-17A) is able to induce the CCL2 expression in Nph. The study aimed to evaluate the IL-17A and CCL2 levels in serum and circulating Nph in patients with ovarian tumors. Methods: The study included 97 ovarian cancer (OC) patients, 30 patients with benign ovarian tumors (BT) and the control (n=22). The levels of IL-17A (LLC "Cytokine", Russia) and CCL2 (Vector-Best-Volga, Russia) in serum and Nph lysate were assessed by ELISA. The systemic inflammation was assessed by neutrophil to lymphocyte ratio (NLR). Informed voluntary consent was obtained from all women. Statistical processing was performed using one-way ANOVA, Spearman correlations (Statistica 13.0 (TIBCO, USA)). Results: We found an increase in NLR in BT (4.3 ± 1.0) compared with the control (2.2 ± 0.1) (p = 0.020), a decrease in stage I-II OC (2.4 ± 0.2) compared with BT (p = 0.053), and an increase in stage III (4.5 ± 0.9) and IV (4.6 ± 0.5) compared with stage I-II OC (p = 0.054 and p = 0.046, respectively). The cytokines levels are presented in Table. The serum level of IL-17A in BT was higher than in the control (p = 0.010). In stage I-II OC, the serum IL-17A level was decreased in comparison with the BT (p = 0.004). In stage IV OC, the serum IL-17A was higher than in stage I-II (p = 0.015) and the control (p = 0.017). The level of IL-17A in Nph in BT did not differ from the control. In all stages of the OC, the IL-17A Nph level was lower than in the control (p1, 2, 3 = 0.0001). In stage IV OC, the expression of IL-17A in Nph was lower compared with stage III (p = 0.031). The serum and Nph levels of IL-17A were correlated only in stage I-II OC (r = 0.679, p = 0.011). The CCL2 serum levels in BT (p = 0.0002) and OC stage I-II, III, IV were higher compared with the control (p1 = 0.031, p2 = 0.001, p3 = 0.0005, respectively). The Nph CCL2 level was higher in BT than in the control (p = 0.001). In stage I-II OC, the expression of CCL2 in Nph was higher than in the control (p = 0.034), but lower than in the BT (p = 0.003). In OC stages III and IV, the Nph CCL2 level was higher than in the control, but did not differ from that in BT and stages I-II. In stage III OC, the CCL2 level in Nph negatively correlated with the serum IL-17A level (r = -0.405, p = 0.049). Conclusions: The pro-tumor polarization of circulating Nph is not IL-17A-dependent in patients with ovarian tumors. The patterns of the systemic immune response differ in benign ovarian tumors, early, and advanced ovarian cancer.[Table: see text]

Dyslipidemia among allergic rhinitis patients: Frequency and risk factors

BackgroundAlthough cumulative data strongly suggest an association between dyslipidemia and allergic disorders, especially asthma, evidence regarding allergic rhinitis (AR) is lacking. We aimed to assess frequency and associated risk factors of dyslipidemia among patients with AR. MethodsThe current study is a cross-sectional study that recruited 150 AR patients by systematic randomization. Blood samples for serum lipid profile, total immunoglobulin E (IgE) and serum interleukin-17A (IL-17A) were withdrawn from all patients. ResultsDyslipidemia was prevalent in 84 AR patients (56%). Higher levels of total IgE, IL17-A, and sensitization to hay dust and mixed mites significantly increased the risk of dyslipidemia among AR patients by 1.004, 1.062, 4.057 and 3.652 respectively (P < 0.05). ConclusionHigh serum total IgE level, high serum IL-17A level, and sensitization to hay dust and mixed mites are independent risk factors for dyslipidemia among AR patients.

MicroRNA profiling in Chinese children with Henoch-Schonlein purpura and association between selected microRNAs and inflammatory biomarkers.

This study aimed to profile the microRNA levels in Chinese Henoch-Schonlein purpura (HSP) children and to explore their association with inflammatory factors and T helper 17 (Th17)/regulatory T (Treg). Forty-five HSP children and 27 healthy controls were enrolled in this study, and microRNA levels were profiled with a microRNA microarray. The levels of selected microRNAs were determined by quantitative real-time PCR, and the levels of serum IgA, interleukin-6, interleukin-10 and interleukin-17A were detected by enzyme-linked immunosorbent assay. Additionally, Th17 and Treg cells were analysed by flow cytometry. There were 9 up-regulated and 27 down-regulated microRNAs in the PBMCs of Chinese HSP children. Among them, miR-1-3p, miR-19b-1-5p and miR-29b-1-5p were up-regulated, while miR-483-5p and miR-1246 were down-regulated. Additionally, these selected microRNAs could differentiate HSP patients from healthy controls. Interestingly, miR-29b-1-5p was correlated with IgA, miR-19b-1-5p, miR-483-5p and miR-1246 were correlated with interleukin-6, while miR-1-3p and miR-1246 were correlated with Th17/Treg. This study reveals that the altered microRNAs could differentiate HSP from the healthy, and were associated with inflammatory factors or Th17/Treg. It is indicated that alteration in these microRNAs may contribute to the HSP pathogenesis and may become therapeutic targets or diagnostic biomarkers for HSP.

Serum interleukin-6, interleukin-17A, and tumor necrosis factor-alpha in patients with recurrent aphthous stomatitis.

Recurrent aphthous stomatitis remains the most common disease of the oral mucosa. The aim of this study was to investigate the clinical significance of serum interleukin-6, interleukin-17A, and tumor necrosis factor-alpha in recurrent aphthous stomatitis. Using flow cytometry analysis, we detect the level of serum interleukin-2, interleukin-6, interleukin-17A, tumor necrosis factor-alpha, and interferon-gamma in 127 patients with recurrent aphthous stomatitis and 20 healthy control cases; compare; and analyze the correlation of each index. The levels of serum interleukin-2, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma in the recurrent aphthous stomatitis group were higher than in the control group, and the differences were statistically significant (P<.05). There was no significant difference in interleukin-17A between the two groups. The levels of serum interleukin-6 and tumor necrosis factor-alpha in recurrent aphthous stomatitis patients were significantly increased. Considering that serum TNF-α was mostly within the normal range, its role in the pathology of RAS needed to be further explored.

Serum interleukin-17A level after on-pump coronary artery bypass grafting surgery

Serum interleukin-17A level after on-pump coronary artery bypass grafting surgery

Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice

BackgroundThe R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD.MethodsIn this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression.ResultsDopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice.ConclusionsThese findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD.

A Novel Selective Sphingosine Kinase 2 Inhibitor, HWG-35D, Ameliorates the Severity of Imiquimod-Induced Psoriasis Model by Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes.

Sphingosine kinases (SK) catalyze the phosphorylation of sphingosine to generate sphingosine-1-phosphate. Two isoforms of SK (SK1 and SK2) exist in mammals. Previously, we showed the beneficial effects of SK2 inhibition, using ABC294640, in a psoriasis mouse model. However, ABC294640 also induces the degradation of SK1 and dihydroceramide desaturase 1 (DES1). Considering these additional effects of ABC294640, we re-examined the efficacy of SK2 inhibition in an IMQ-induced psoriasis mouse model using a novel SK2 inhibitor, HWG-35D, which exhibits nM potency and 100-fold selectivity for SK2 over SK1. Topical application of HWG-35D ameliorated IMQ-induced skin lesions and normalized the serum interleukin-17A levels elevated by IMQ. Application of HWG-35D also decreased skin mRNA levels of interleukin-17A, K6 and K16 genes induced by IMQ. Consistent with the previous data using ABC294640, HWG-35D also blocked T helper type 17 differentiation of naïve CD4+ T cells with concomitant reduction of SOCS1. Importantly, HWG-35D did not affect SK1 or DES1 expression levels. These results reaffirm an important role of SK2 in the T helper type 17 response and suggest that highly selective and potent SK2 inhibitors such as HWG-35D might be of therapeutic use for the treatment of psoriasis.

Serum interleukin-17A/interferon-gamma ratio as a predictor for the severity of atrial low voltage in atrial fibrillation: from FIB-MARK study

Abstract Background Atrial fibrosis is hallmark of structural remodeling in atrial fibrillation (AF), but the inflammatory mechanism remains unclear. The purpose of the present study was to identify the specific inflammatory biomarkers to atrial fibrosis evaluated by atrial low voltage (LV) in AF patients for clarification of the mechanism. Methods Forty inflammatory biomarkers were quantified in 16 consecutive AF patients measured left atrial low voltage during catheter ablation. Results Median %LV area was 17%. In Pearson's correlation analysis, interleukin (IL)-17A and interferon (IFN)-γ was the most significant positive and negative correlation with %LV (R=0.35 and 0.43, P&amp;lt;0.001). Furthermore, there was a significant correlation between IL-17A/IFN-γ ratio and %LV (R=0.65, P=0.007). The area under the receiver operator characteristics curve of IL-17A/IFN-γ ratio for significant LV (%LV &amp;gt;10% as a reference standard) was 0.88. IL-17A/IFN-γ ratio was significantly higher in patients with significant LV than those without (1.41 versus 0.97, P=0.01), Furthermore, the sensitivity, specificity, and accuracy for detecting significant LV were 60%, 100%, and 75.0% at the cutoff value of 1.3. The event free survival from recurrent atrial tachyarrhythmias was not significantly different between patients with and without IL-17A/IFN-γ ratio &amp;gt;1.3 (83.3% versus 80.0% at 1-year, P=0.81). Conclusions Among inflammatory biomarkers, IL-17A/IFN-γ ratio was a significant predictor for the severity of left atrial low voltage n AF patients. Further study is needed to reveal the association between IL-17A and IFN-γ for development of fibrosis in AF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI GrantNumber JP19K17594

Serum interleukin 17A and interleukin 17F in children with inflammatory bowel disease

Interleukin 17A (IL-17A) and interleukin 17F (IL-17F) appear to play important role in pathogenesis of some autoimmune diseases. However, their role in inflammatory bowel disease (IBD) has not been yet fully elucidated. We aimed to determine serum IL-17A and IL-17F in children with IBD and to assess their association with IBD activity. Recruited children underwent blood tests including complete blood count, C-reactive protein, erythrocyte sedimentation rate, IL-17A and IL-17F and stool sampling for calprotectin. The study group comprised 68 children with IBD, including 43 with ulcerative colitis and 25 with Crohn’s disease. Control group included 20 healthy children. IL-17A was significantly increased in children with IBD (median: 10.95 pg/ml; range: 0.65–200.54 pg/ml) compared to controls (median: 4.09 pg/ml; range: 0.67–26.20 pg/ml) (p = 0.002). IL-17A was significantly increased in patients with active phase of ulcerative colitis (median: 14.58 pg/ml; range: 0.65–200.54 pg/ml) compared to those in ulcerative colitis remission (median: 8.13 pg/ml; range: 1.61–58.56 pg/ml) (p = 0.04). There were no significant differences in IL-17A among patients with active and inactive Crohn’s disease (p = 0.18). IL-17F did not differ significantly between children with IBD (median: 15.11 pg/ml; range: 0.09–189.84 pg/ml) and controls (median: 11.56 pg/ml; range: 0.19–32.49 pg/ml) (p = 0.33). Our study suggests that interleukin 17A may diverse active phase from remission only in ulcerative colitis but not in Crohn’s disease.

Elevated Levels of Serum IL-17A Secondary to Repeated Intravitreal Injections of Aflibercept in Treatment-Naive Patients with Neovascular Age-Related Macular Degeneration

We evaluated the effect of three monthly intravitreal injections of aflibercept on the serum concentration of interleukin 17A (IL-17A), monocyte chemoattractant protein 1 (MCP-1/CCL2), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in treatment-naive patients with neovascular age-related macular degeneration (nAMD). Twenty-two eyes of twenty-two patients with nAMD scheduled for the initial loading phase of intravitreal aflibercept (2 mg/0.05 mL) were included. Serum VEGF, PlGF, MCP-1/CCL2 and IL-17A levels were determined four times in each individual—just before the first injection, 2–3 days after the first injection, just before the third injection, and then 2–3 days after the third aflibercept injection. A statistically significant difference was found between the serum PlGF and IL-17A levels measured before the first injection and after the initial loading phase, with a mean value (MV) of 440.884 vs. 302.151 (p = 0.023) for PlGF and MV = 139.088 pg/mL vs. 151.233 pg/mL (p = 0.016) for IL-17A, respectively. There were no statistically significant differences for VEGF and MCP-1/CCL2 between any of the compared measurements. We reveal that repeated injections of aflibercept promote an increase in serum IL-17A concentration, which may lead to a systemic inflammatory response mediated by IL-17A, but not by MCP-1.

MiR-1-3p facilitates Th17 differentiation associating with multiple sclerosis via targeting ETS1.

T helper 17 (Th17) cells are involved in the pathogenesis of multiple sclerosis (MS). The present study aimed to explore the role of miR-1-3p in Th17 cell differentiation associated with MS. PATIENTSAND METHODS: Expression of miR-1-3p in periphery blood mononuclear cells (PBMC), cerebrospinal fluid (CSF), CD4+ T cells, CD8+ T cells, non-T cells and differentiated CD4+ T cells derived from healthy donors and MS patients during remitted and relapsed stages was detected. Level of ETS1 in PBMC in MS-relapse patients was examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlations among neurofilament light (NF-L), C-reactive protein (CRP), estrogen receptor 1 (ESR), interleukin 17A (IL-17A) in serum, NF-L, C-X-C motif chemokine ligand 13 (CXCL13), chitinase 3 like 1 (CHI3L1), RAR related orphan receptor C (RORC) in CSF, and ETS proto-oncogene 1 (ETS1), RORC in PBMC and miR-1-3p expression were analyzed. The target gene of miR-1-3p was analyzed by performing Dual-Luciferase reporter assay, and the IL-17A+ CD4+ (Th17) cells were detected by flow cytometer. Gene expressions of IL-17A, RORC and Th17 pathogenic were determined by qRT-PCR. Upregulated miR-1-3p was observed in MS-relapse patients and Th17 cells, and expression of miR-1-3p was positively correlated with MS severity. MiR-1-3p overexpression in naïve CD4+ T cells promoted the differentiation of Th17 cells by upregulating the level of inflammation-associated markers. The expression of ETS1, which was predicted to be the target gene of miR-1-3p, was reduced in PBMC from MS-relapse patients, while the upregulation of ETS1 inhibited the expression of pathogenic genes of Th17. The study demonstrated the positive role of miR-1-3p in Th17 differentiation associated with MS via targeting ETS1.

Low Serum IL-17A in Pregnancy During Second Trimester Is Associated With an Increased Risk of Subclinical Hypothyroidism

Problem: Interleukin-17A (IL-17A) has a role in sustaining normal pregnancy. IL-17A is also associated with thyroid autoimmunity during pregnancy. This study sought to investigate whether IL-17A is a risk factor for thyroid dysfunction during pregnancy in women negative for thyroid autoantibodies.Methods of Study: The study comprised 216 pregnant women with negative thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) during the second trimester who provided blood samples for serum IL-17A, thyroid autoantibodies and thyroid function tests. To further evaluate the ratio of CD4+IL-17A+ Th17 cells, we collected peripheral blood from 26 women with thyroid-stimulating hormone (TSH) levels ≤ 2.5 mIU/L and 26 pregnancy-week matched women with TSH levels >2.5 mIU/L, along with samples from 20 women with TSH levels ≤ 4 mIU/L and 20 pregnancy-week matched women with TSH levels >4 mIU/L.Results: The serum IL-17A levels and ratios of CD4+IL-17A+ cells were significantly lower in women with TSH > 2.5 mIU/L than in those with TSH ≤ 2.5 mIU/L (both P < 0.01). Similar lower differences were noted in women with TSH > 4 mIU/L than in those with TSH ≤ 4 mIU/L (both P < 0.01). Moreover, serum TSH correlated negatively with IL-17A levels (β = −0.195, P = 0.004), but positively with the week of gestation (β = 0.284, P < 0.001). Logistic regression indicated that a lower serum IL-17A level was a risk factor for TSH > 2.5 mIU/L [OR = 0.453 (0.298–0.689), P = 0.000] and TSH > 4.0 mIU/L [OR = 0.588 (0.385–0.899), P = 0.013].Conclusion: A low serum IL-17A level during the second trimester is associated with an increased risk of TSH > 2.5 mIU/L and subclinical hypothyroidism.

Elevated Interleukin-17A expression in amlodipine-induced gingival overgrowth.

Amlodipine, a calcium channel blocker derivative, is frequently used by patients with high blood pressure. Studies reported that it can induce gingival overgrowth. However, the underlying mechanism is not fully described yet. Interleukin-17A (IL-17A) is known as a proinflammatory cytokine, but current studies indicate that it has a role in fibrotic disorders and epithelial-mesenchymal transition (EMT). The aim of this study was to figure out the possible role of IL-17A in amlodipine-induced gingival overgrowth. Twenty-nine (29) individuals participated in the study, and they were assigned into 3 groups based on medical status and clinical periodontal examination; 9 patients with amlodipine-induced gingival overgrowth, 11 patients with inflammatory gingival overgrowth, and 9 healthy individuals as a control group. Clinical periodontal parameters including plaque index (PI), gingival index (GI), and gingival overgrowth index (GOI) were recorded. Blood and gingival crevicular fluid (GCF) samples were obtained. Gingival tissues were taken by appropriate periodontal surgery following initial periodontal therapy. To detect IL-17A on tissue samples, immunohistochemistry (IHC) was performed. Quantitative analysis was done, and the expression level of IL-17A was given as the percent positively stained cells. Enzyme-linked immunosorbent assay (ELISA) kits were used to analyze IL-17A in serum and GCF samples. All recorded clinical parameters were significantly higher in gingival overgrowth groups compared with control. Evaluation of inflammation on tissue sections did not show any significant change within the groups. Immunohistochemistry findings showed that IL-17A expression was increased in amlodipine samples (81.90%) compared with control samples (42.35%) (P<.001). There was an increase in the inflammatory group (66.08%) which is significantly less than the amlodipine group (P<.05). IL-17A levels in serum and GCF samples were not different within the study groups. In this study, elevated IL-17A expression regardless of inflammation shows that amlodipine might cause an increase of IL-17A in gingival tissues. This increase might induce fibrotic changes and EMT in gingival overgrowth tissues. The association of IL-17A with fibrosis and EMT in gingival tissues requires further investigation.

Clinical Role of Serum Interleukin-17A in the Prediction of Refractory Mycoplasma pneumoniae Pneumonia in Children.

BackgroundMycoplasma pneumoniae pneumonia (MPP) is a common community-acquired pneumonia (CAP) in children, which may become refractory MPP (RMPP) to treatment.ObjectiveThe purpose of this study was to evaluate the clinical utility of measuring serum interleukin (IL)-17A to predict RMPP.Patients and MethodsA retrospective clinical study at a single pediatric center included a review of the medical records of all children hospitalized for CAP between November 2015 and October 2019. The diagnosis of MPP was based on clinical presentation, chest radiography, and measurement of serum anti-Mycoplasma immunoglobulin IgM antibody titer using the microparticle agglutination method or sputum samples for Mycoplasma pneumoniae by PCR. Serum levels of IL-18 and IL-17A were determined by ELISA.ResultsOf the 625 children diagnosed with CAP, there were 154 children with MPP and without underlying diseases who were divided into a non-refractory MPP (NRMPP) group (n = 109) and a RMPP group (n = 45). The RMPP group had a higher incidence of tachypnea, cyanosis, hypoxia, segmental or lobar pneumonia, pleural effusion, and a longer period of hospitalization compared with NRMPP group (all P-values < 0.05). A serum IL-17A level above 10.8 pg/mL was a predictor for RMPP: area under the curve (AUC) 0.822; standard error (SE) 0.039; 95% confidence interval (CI) 0.746–0.897; diagnostic sensitivity and specificity of 77.8% and 77.1%, respectively. An LDH level above 436.5 IU/L and an IL-18 level above 464.5 pg/mL were the second most useful markers for RMPP: AUC 0.775, 0.775; SE 0.038, 0.039; 95% CI 0.700–0.850, 0.698–0.852; sensitivity 77.8%, 82.2%; specificity 62.4%, 59.6%; respectively.ConclusionThis preliminary study of MPP in a pediatric population has shown that measurement of serum IL-17A may be a useful marker for the predictor of RMPP.