Research progress on roles of IL-17A in sepsis related organ injury / 中华临床感染病杂志

Sepsis is a pathological condition in which the body’s response to infection is dysfunctional and may lead to life-threatening organ failures as one of the leading causes of death worldwide. However，there is still a lack of effective prevention and treatment for sepsis. IL-17A is an inflammatory cytokine produced primarily by activated T cells and is involved in host defense，tissue repair，the pathogenesis of inflammatory diseases，and the progression of cancer. This article reviews the recent research progress on the roles of IL-17A in sepsis-related organ damage，and its potentials as a novel therapeutic target for the clinical treatment of sepsis.

Youguiwan Reduces Airway Inflammation in COPD Rats with Syndrome of Kidney-Yang Deficiency by Inhibiting Leptin/JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Youguiwan on the leptin/Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） due to kidney-Yang deficiency. MethodForty rats were modeled for COPD with the syndrome of kidney-Yang deficiency by intratracheal instillation of lipopolysaccharide on day 1 and day 14 and continuous fumigation for 6 weeks， during which hydrocortisone was injected intramuscularly at an interval of 3 days. The modeled rats were randomized into model， high- （11.7 g·kg-1）， medium- （5.85 g·kg-1）， and low-dose （2.93 g·kg-1） Youguiwan， and aminophylline （0.054 g·kg-1） group. In addition， 8 SD rats were set as the blank group. After the completion of modeling， the rats in each group were administrated with the corresponding drug by gavage for 28 consecutive days. After the last administration， samples were collected. A lung function analyzer was used to evaluate the lung function of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-17A （IL-17A）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the bronchoalveolar lavage fluid （BALF）. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung tissue， and Masson staining was employed to observe the deposition of blue collagen fibers around bronchi in the lung tissue and calculate the inflammation score. The immunofluorescence assay was employed to measure the protein content of collagen type Ⅰ （ColⅠ） and α-smooth muscle actin （α-SMA） in the bronchi. The protein and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed decreased lung function （P<0.01）， elevated levels of IL-6， IL-17A， and TNF-α in the BALF （P<0.01）， and increased lung inflammation score， deposition of subcutaneous collagen fibers in the airway， and ColⅠ and α-SMA proteins （P<0.01）. Furthermore， the modeling up-regulated the proteins and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue （P<0.01） and enhanced the phosphorylation of JAK2 and STAT3 （P<0.01）. Compared with the model group， high- and medium-dose Youguiwan improved the lung function， decreased the inflammation score， reduced collagen fiber deposition and ColⅠ and α-SMA proteins， lowered the levels of IL-6， IL-17A， and TNF-α in the BALF， down-regulated the mRNA and protein levels of leptin， JAK2， STAT3， and IL-17A， and weakened the phosphorylation of JAK2 and STAT3 （P<0.05， P<0.01）. The aminophylline group had higher IL-17A and TNF-α levels than the high-dose Youguiwan group， lower IL-17A level than the medium and low-dose Youguiwan groups， and lower TNF-α level than the low-dose Youguiwan group. Compared with the aminophylline group， the high- and medium-dose Youguiwan groups showed reduced deposition of collagen fibers and protein levels of ColⅠ and α-SMA around the bronchi in the lung tissue （P<0.05， P<0.01）， decreased inflammation score， and down-regulated protein and mRNA levels of leptin， JAK2， STAT3， and IL-17A in the lung tissue. ConclusionYouguiwan can prevent airway remodeling by inhibiting IL-17A to reduce inflammation and collagen deposition in COPD rats， which may be related to the inhibition of the leptin/JAK2/STAT3 signaling pathway.

Relationship between serum MBL,HRG,IL-23/IL-17 inflammatory axis and cerebral vasospasm and prognosis in patients with aneurysmal subarachnoid hemorrhage after interventional embolization / 国际检验医学杂志

Objective To investigate the relationship between serum mannan binding lectin(MBL),histi-dine rich glycoprotein(HRG),interleukin(IL)-23/IL-17 inflammatory axis and cerebral vasospasm(CVS)and prognosis in patients with aneurysmal subarachnoid hemorrhage(aSAH)after interventional emboliza-tion.Methods A total of 195 patients with aSAH who underwent interventional embolization treatment in the hospital from March 2019 to February 2022 were selected and were divided into no CVS group(126 cases),mild CVS group(18 cases),moderate CVS group(39 cases),and severe CVS group(12 cases)according to the occurrence and severity of CVS detected by digital subtraction angiography at the 4th postoperative day.The levels of serum MBL,HRG,IL-23 and IL-17 among the four groups before and 3 d after surgery were compared.The patients were followed up for 6 months and divided into good prognosis group(137 cases)and poor prognosis group(58 cases)according to their prognosis.Factors influencing poor prognosis in aSAH pa-tients were analyzed by multivariate Logistic regression model.The predictive value of serum MBL,HRG,IL-23,IL-17 levels and their combined application models for poor prognosis in patients with aSAH was analyzed by receiver operating characteristic(ROC)curve.Results The incidence rate of CVS after interventional em-bolization was 35.38%in 195 patients with aSAH.3 d after surgery,the serum levels of MBL,IL-23 and IL-17 in the mild,moderate,and severe CVS groups were higher than those in the no CVS group,those in the severe CVS group were higher than those in the moderate CVS group,those in the moderate CVS group were higher than those in the mild CVS group(P<0.05).The serum HRG levels in the mild,moderate,and severe CVS groups were lower than those in the non CVS group,those in the severe CVS group were lower than those in the moderate CVS group,those in the moderate CVS group were lower than those in the mild CVS group(P<0.05).3 d after surgery,the levels of serum MBL,IL-23 and IL-17 in the four groups were higher than that before surgery,while the levels of serum HRG were lower than that before surgery(P<0.05).The pro-portions of patients with aneurysm diameter≥6 mm,number of aneurysms>1,surgery time>24 h,Hunt-Hess grade Ⅲ/Ⅳ and postoperative CVS,and serum levels of MBL,IL-23,and IL-17 on the 3rd day after sur-gery in the good prognosis group were lower than those in the poor prognosis group,and serum HRG levels at 3 d after surgery in the good prognosis group were higher than that in the poor prognosis group(P<0.05).Multivariate Logistic regression analysis showed that aneurysm diameter≥6 mm,Hunt-Hess grade Ⅲ/Ⅳ and postoperative CVS,elevated serum levels of MBL,IL-23,and IL-17 and decreased HRG level at 3 d after sur-gery were independent risk factors for poor prognosis in aSAH patients(P<0.05).ROC results showed that serum levels of MBL,HRG,IL-23,and IL-17 at 3 d after surgery had certain predictive power for poor progno-sis in patients with aSAH.The predictive model with the combined application of four indicators had relatively high efficiency(the area under the curve was 0.853).Conclusion Elevated levels of MBL,IL-23,IL-17,and decreased HRG levels in aSAH patients after interventional embolization could increase the risk of CVS and are associated with poor prognosis in aSAH patients after interventional embolization.The above indicators have a certain predictive power for poor prognosis in aSAH patients.

Correlation between IL-17 gene polymorphism and type 2 diabetes mellitus in Han population in southeast Shanxi Province / 实用医学杂志

Objective To determine the correlation between single-nucleotide polymorphisms of IL-17 with type 2 diabetes in Han population in southeastern Shanxi Provincein.Methods The basic information and related clinical data of the subjects were collected of normal healthy controls and T2DM.Whole blood DNA was extracted,and IL-17 polymorphisms(rs2275913,rs3819024,rs4711998 and rs8193036)were analyzed by using a polymerase chain reaction-high temperature ligase reaction.Results There was no significant difference in the genotype and allele frequency distribution of the four SNP loci of IL-17 gene between the two groups(P>0.05).IL-17 polymorphism was not linked with T2DM in multiple genetic models after controlling for age,BMI,WC,and dyslipidemia(P>0.05).Further analysis showed that the levels of AA genotype was substantially lower of FPG and HOMA-IR levels when compared with the AG and GG genotypes,and the differences among the three groups were statistically significant(P<0.05).However,BMI,FINS,HbA1c and HOMA-βwas no statistical significance among the three groups(P>0.05).Besides,WC and HOMA-IR of AA genotype(rs3819024)were notable higher than those of GG genotype in T2DM group(P<0.05).Conclusions The IL-17 gene polymorphisms rs2275913,rs3819024,rs4711998,and rs8193036 in the Han population of southeast Shanxi Province may not be associated with T2DM.In this region Han T2DM patients,AA genotype at rs2275913 of the IL-17 gene is associ-ated to FPG and HOMA-IR,while GG genotype at rs3819024 is related to WC and HOMA-IR,which could be the potential genotype of IL-17 impacting glucose metabolism.

Effect of Xuanfei Zhisou Prescription on IL-17 Signaling Pathway in COPD Model Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Xuanfei Zhisou prescription on the interleukin-17 （IL-17） signaling pathway in model rats with chronic obstructive pulmonary disease （COPD）. MethodA total of 60 Wistar rats were randomly divided into a blank group （10 rats） and a model group （50 rats）， and COPD model rats were established by tracheal infusion of lipopolysaccharide combined with passive fumigation. After modeling， the rats were divided into the model group， dexamethasone group， and high， medium， and low-dose Xuanfei Zhisou prescription groups （3.6， 1.8， 0.9 g·kg-1·d-1） according to the random number table. Rats in the blank group and model group were given normal saline of 10 mL·kg-1·d-1 by gavage administration， and the intervention groups of Xuanfei Zhisou prescription were given corresponding drugs. Rats in the dexamethasone group were given dexamethasone of 2.57×10-4 g·kg-1·d-1 for 28 days. The level of pulmonary function indexes in rats was measured by a pulmonary function detector. The contents of interleukin-6 （IL-6）， interleukin-8 （IL-8）， IL-17， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expressions of IL-17A， IL-17RA， nuclear factor-κB activator 1 （Act1）， tumor necrosis factor-associated factor 6 （TRAF6）， p-p38 mitogen-activated protein kinase （p-p38 MAPK）， nuclear factor-κB p65 （NF-κB p65）， and phosphorylation were detected by immunohistochemistry （IHC）. The protein expression levels of IL-17A， IL-17RA， Act1， and TRAF6 in the lung tissue were detected by Western blot. The mRNA expressions of IL-17A， IL-17RA， Act1， and TRAF6 in the lung tissue were detected by Real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the serum contents of IL-6， IL-8， IL-17， IL-1β， and TNF-α in the model group were significantly increased （P<0.05）， and the flow rate and volume indexes of pulmonary function in the model group were significantly decreased （P<0.05）， while the time indexes and other indexes were significantly increased （P<0.05）. The mRNA and protein expression levels of IL-17A， IL-17RA， Act1， and TRAF6 in pulmonary tissue and the positive expressions of downstream NF-κB p65， p-NF-κB p65， and p-p38 MAPK were increased （P<0.05）. Compared with the model group， the levels of IL-6， IL-8， IL-17， IL-1β， and TNF-α in the serum of all treatment groups were decreased to varying degrees （P<0.05）， and the indexes of pulmonary function were improved to different degrees （P<0.05）. The mRNA and protein levels of IL-17A， IL-17RA， Act1， and TRAF6 and the positive expression of downstream NF-κB p65， p-NF-κB p65， and p-p38 MAPK in high and medium-dose Xuanfei Zhisou prescription groups were significantly decreased （P<0.05）. ConclusionXuanfei Zhisou prescription can effectively resist inflammation of COPD rats. The mechanism may be related to down-regulating the protein expression of IL-17A， IL-17RA， Act1， and TRAF6， inhibiting downstream NF-κB and p38 MAPK signaling pathways， and reducing the release of IL-6， IL-8， TNF-α， IL-17， and IL-1β， thus reducing the airway inflammation response.

The relationship between serum interleukin-17A, chemokine ligand 19 levels and disease activity in patients with lupus nephritis / 中国医师进修杂志

Objective:To investigate the relationship between serum levels of interleukin-17A (IL-17A) and chemokine ligand 19 (CCL19) and disease activity in patients with lupus nephritis.Methods:A total of 100 patients with lupus nephritis admitted to Affiliated Hospital of Jining Medical College from June 2020 to February 2023 were collected as the disease group, according to the disease activity index, patients were grouped into inactive group (32 cases), mild active group (21 cases), moderate active group (29 cases), and severe active group (18 cases); another 100 healthy individuals who underwent physical examinations in our hospital during the same period were collected as the control group. Enzyme linked immunosorbent assay (ELISA) was applied to detect the expression levels of IL-17A and CCL19 in serum; Pearson method was applied to analyze the correlation between serum IL-17A, CCL19 and routine indicators in patients with lupus nephritis; receiver operating characteristic curve was applied to analyze the diagnostic value of serum IL-17A and CCL19 for moderate/severe lupus nephritis disease activity.Results:The expression levels of IL-17A and CCL19 in the serum of the disease group were obviously higher than those of the control group: (252.63 ± 64.47) ng/L vs. (123.27 ± 25.12) ng/L and (566.98 ± 73.36) ng/L vs. (275.63 ± 50.48) ng/L ( t = 18.70 and 32.72, P<0.05); the serum levels of IL-17A and CCL19 in the severe active, moderate active, and mild active groups were higher than those in the inactive group: (331.42 ± 87.46), (278.50 ± 74.19) and (232.34 ± 59.16) ng/L vs. (198.18 ± 46.22) ng/L; (662.33 ± 89.57), (606.14 ± 79.25) and (552.84 ± 68.36) ng/L vs. (487.13 ± 62.19) ng/L, and with the increase of disease activity, the levels of serum IL-17A and CCL19 gradually increased ( F = 17.86 and 25.35, P<0.05); the glomerular filtration rate, albumin, complement C 3 and complement C 4 in the active group were obviously lower than those in the inactive group: (69.17 ± 13.25) ml/(min·1.73 m 2) vs. (86.18 ± 14.16) ml/(min·1.73 m 2), (24.18 ± 5.11) g/L vs. (31.25 ± 6.35) g/L, (432.35 ± 95.22) mg/L vs. (675.42 ± 125.16) mg/L, (76.58 ± 17.51) mg/L vs. (121.42 ± 27.18) mg/L, while blood creatinine, urine protein and erythrocyte sedimentation rate were obviously higher than those in the inactive group: (92.34 ± 16.24) μmoI/L vs. (53.21 ± 9.17) μmoI/L, (3.43 ± 0.82) g/24 h vs. (1.26 ± 0.23) g/24 h, (66.37 ± 12.28) mm/1 h vs. (35.62 ± 8.67) mm/1 h ( t = 5.86, 5.97, 10.74, 9.93, 12.70, 14.67 and 12.74; P<0.05); serum IL-17A and CCL19 in patients with lupus nephritis were negatively correlated with glomerular filtration rate, albumin, complement C 3, and complement C 4, while positively correlated with blood creatinine, urine protein, and ESR ( P<0.05); the area under the curve (AUC) of the combined diagnosis of serum IL-17A and CCL19 for lupus nephritis disease activity was 0.961, which was superior to their respective individual diagnoses ( Z = 2.24 and 3.16, P = 0.025 and 0.002). Conclusions:The expression levels of IL-17A and CCL19 in serum gradually increase with the increase of disease activity in patients with lupus nephritis. The combined detection of the two has good diagnostic value for disease activity in lupus nephritis.

Role of Interleukin-17 family cytokines in disease severity of patients with knee osteoarthritis

Abstract Background Interleukin-17 (IL-17) family plays a role in the pathogenesis of knee osteoarthritis (KOA) by contributing to the inflammatory and destructive processes in the affected joint. This study aimed to measure levels of IL-17 A and IL-25 (IL-17E) in serum of KOA patients and determine their roles in the disease severity of patients. Methods In this, 34 patients with KOA and 30 age and sex-matched healthy subjects (HS) were enrolled. Patients were categorized based on their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS), and Body Mass Index (BMI) scores. The enzyme-linked immunosorbent assay (ELISA) technique was employed to measure serum levels of IL-17 A and IL-25. Results Level of IL-25 was significantly higher (P < 0.0001) in the KOA subjects than HS. IL-17 A level was significantly higher in KOA cases with WOMAC < 40 (P < 0.0001) in comparison to HS. IL-25 level was significantly higher in the KOA cases with WOMAC < 40 (P < 0.0001) and with WOMAC ≥ 40 (P < 0.0001) compared to HS. IL-17 A concentration was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) compared to HS. IL-25 level was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) and with VAS ≥ 5 (P < 0.0001) in comparison to HS. KOA patients with BMI ≥ 30 had significantly higher IL-17 A and IL-25 concentration in comparison to HS. Conclusions The serum level of IL-25 in KOA patients is increased probably due to negative controlling feedback on inflammatory responses, which can be associated with obesity and disease activity.

Genetic polymorphism of interleukins 6 and 17 correlated with apical periodontitis: A Cross-sectional study

Abstract Interleukins 6 and 17 act in bone resorption in the presence of infections of endodontic origin for host defense. Genetic polymorphisms may be associated with increased bone loss, represented by areas of large periapical lesions. This study aimed to verify the frequency of interleukin 6 and 17 gene polymorphism in patients with asymptomatic apical periodontitis or chronic apical abscess and to verify the existence of correlations between periapical lesion area with age, gender, and presence of the polymorphism, in the studied population, in the state of Pernambuco. A population consisting of thirty diagnosed individuals was included. The area of the lesions was measured in mm². Genomic DNA was extracted and genotyping was performed by Polymerase Chain Reaction Restriction Fragment Length Polymorphism for interleukin 6 (rs 1800795) and interleukin 17 (rs 2275913). Fisher's exact, chi-square, and odds ratio tests were used. A logistic regression analysis was also performed using sex, age, and the presence of polymorphism as covariates, in addition to linear regression to test the relationship between age and lesion area. All tests used a significance level of 0.05% (p ≤0.05%). There was no statistical significance in the occurrence of large areas of periapical lesions correlated with age, sex, and diagnosis, nor in the distribution of alleles in the polymorphism of interleukins 6 and 17 in the studied groups. The frequency of homozygous and heterozygous polymorphism was high. The polymorphism of these interleukins is not correlated with the increase in the areas of asymptomatic periapical inflammatory lesions.

Resumo As interleucinas 6 e 17 atuam na reabsorção óssea na presença de infecções de oriegem endodôntica para defesa do hospedeiro. Polimorfismos genéticos podem estar associados ao aumento da perda óssea, representada por áreas de lesões periapicais grandes. O objetivo deste estudo foi verificar a frequência do polimorfismo dos genes interleucina 6 e 17 em pacientes com periodontite apical assintomática ou abscesso apical crônico e verificar a existência de correlações entre área de lesão periapical com idade, sexo e presença do polimorfismo, na população estudada, no estado de Pernambuco. Foi incluída uma população constituída por trinta indivíduos diagnosticados. A áreas da lesões foram medidas em mm². O DNA genômico foi extraído e a genotipagem realizada por Polimorfismo de Comprimento de Fragmento de Restrição de Reação em Cadeia da Polimerase para interleucina 6 (rs 1800795) e interleucina 17 (rs 2275913). Os testes exato de Fisher, qui-quadrado e odds ratio foram utilizados. Uma análise de regressão logística também foi realizada usando sexo, idade e presença de polimorfismo como covariável, além de regressão linear para testar a relação da idade e área da lesão. Todos os testes utilizaram um nível de significância de 0,05% (p ≤0.05%). Não houve significância estatística na ocorrência das áreas grandes de lesões periapicais correlacionadas com idade, sexo e diagnóstico nem nas distribuições de alelos no polimorfismo das interleucinas 6 e 17 nos grupos estudados. A frequência de polimorfismo homozigoto e heterozigoto foi alta. O polimorfismo dessas interleucinas não está correlacionado ao aumento das áreas das lesões inflamatórias periapicais assintomáticas.

Expression of interleukin-17A in serum of children with intravenous immunoglobulin-resistant Kawasaki disease and its clinical significance / 中国当代儿科杂志

OBJECTIVES@#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.@*METHODS@#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.@*RESULTS@#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).@*CONCLUSIONS@#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.

Expression and clinical significance of IL-17 in idiopathic inflammatory myositis / 中华风湿病学杂志

Objective:In this study, the role of IL-17 in the pathogenesis of idiopathic myositis (IIM) was preliminarily investigated by detecting the expression of IL-17 in the muscle tissues of patients with idiopathic inflammatory myositis (IIM) and normal controls.Methods:Twenty-eight patients (20 in DM group with dermatomyositis and 8 in ASS group with anti-synthase syndrome) who were diagnosed with IIM after muscle biopsy and autoantibody detection in our hospital for the first time from October 2019 to August 2021 were included. Twelve cases with normal muscle tissue matched for age and sex were included as the control group. Western blot and immunohistochemical techniques were used to detect the expression level of IL-17 in muscle tissue, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum IL-6. Mann-Whitney U rank sum test was used to compare the difference of IL-17 expression in muscle tissue between the two groups, and non-parametric test was used for comparison between multiple groups. Chi-square test and Spearman rank correlation analysis were used, and P<0.05 was considered statistically significant. Results:① The expression level of IL-17 in IIM muscle tissue[1.63(1.30, 2.05)pg/ml was higher than that in control group[1.00(0.96, 1.00)pg/ml, and the difference was statistically significant ( Z=-3.52, P<0.001). The difference be-tween DM[1.94(1.58, 2.14)pg/ml] and ASS[1.22(1.04,1.55)pg/ml was statistically significant ( Z=-3.20, P=0.001). ② Compared with healthy control group [4.08(3.01, 5.67)pg/ml, the expression of IL-6 in ⅡM serum[8.88(4.93, 13.64) was high ( Z=-3.01, P=0.003), which was positively correlated with the expression of IL-17 ( r=0.42, P=0.027). ③ The ex-pression of IL-17 in muscle tissue was higher in IIM associated with muscle weakness[1.91(1.56, 2.14) pg/ml vs 1.50(1.04, 2.00)pg/ml] ( Z=-1.38, P=0.020), dysphagia [2.06(1.99, 2.14)pg/ml vs 1.62(1.52, 2.04)pg/ml] ( Z=-2.74, P=0.010) and skin involvement[1.98(1.57, 2.14)pg/ml vs 1.04(0.86, 1.61)pg/ml] ( Z=-3.20, P<0.010), and the differences were statistically significant ( P<0.05). ④IL-17 was positively correlated with Myoact-total activity ( r=0.51, P=0.006), Myoact-muscle symptom ( r=0.45, P=0.016), erythrocyte sedimen tation ( r=0.48, P=0.020), and myoenzyme increase ( r=0.56, P=0.002). Conclusion:IL-17 and IL-6 are synergistically involved in the pathogenesis of IIM, suggesting that IL-17 is the therapeutic target of IIM.

The role of IL-17A in the pathogenesis of primary Sj?gren′s syndrome / 中华风湿病学杂志

Objective:To investigate the role of IL-17A in the regulation of inflammatory factors and autophagy genes of PBMCs in pSS patients.Methods:Thirty patients fulfilled the diagnosis of pSS were selected, 20 mL of peripheral blood was drawn, PBMCs were isolated and divided into the PBMCs group, IL-17A stimulant group and IL-17A inhibitor group. After warm incubation 48 h of immunofluorescence was applied to detect microtubule-associated protein l light chain 3 (LC3), and the ELISA method was used to detect the expression of the inflammatory factors IL-4, IFN-γ, IL-13 expression. Real-time fluorescence polymerase chain reaction (qRT-PCR) was used to detect the expression of autophagy-inducing genes Ambra-1, Bif-1 and apoptosis genes Bcl-2 and Bcl-XL mRNA, and immunoprotein blotting was used to detect the expression of Beclin1 and LC3 protein. ANOVA was used to compare the differences between groups, and t-test was used for two-by-two comparisons. Results:The immunofluorescence results showed a significant increase in LC3 autophagic vesicles in the IL-17A inhibited group compared with the IL-17A stimulator group. The ELISA results showed that, compared with the PBMCs group [IL-4: (13.39±0.32) pg/ml, IFN-γ: (14.4±0.4) pg/ml, and IL-13: (854±36) pg/ml], IL-4 secretion in the IL-17A stimulated group (11.54±0.30) was decreased ( t=12.83, P=0.024), IFN-γ and IL-13 secretion [(17.6±0.4), (908±51) pg/ml] were increased ( t=19.35, P=0.033; t=2.55, P=0.020); compared with IL-17A inhibitor group [IL-4: (15.65±0.26) pg/ml, IFN-γ: (13.6±0.3) pg/ml, and IL-13: (792±57) pg/ml]. Compared with the IL-17A stimulator group, IL-4 secretion was decreased ( t=21.31, P=0.006), and IFN-γ and IL-13 expression was increased ( t=17.34, P=0.015; t=5.14, P=0.007). The PCR results showed that, compared with Ambra-1, Bif-1, Bcl-2, and Bcl-XL mRNA expression (5.61±0.33, 5.04±0.60, 1.28±0.09, 1.56±0.03) in the PBMCs group, Ambra-1, Bif-1 mRNA in the IL-17A-stimulated group expression (3.76±0.24, 4.68±0.41) were down-regulated ( t=14.30, P=0.007; t=15.02, P=0.012), and Ambra-1, Bif-1 mRNA expression (7.91±1.17, 9.30±0.25) were increased in the IL-17A inhibition group, ( t=13.59, P=0.025; t=11.54, P=0.031), anti-apoptotic proteins Bcl-2, Bcl-XL mRNA expression (1.75±0.06, 2.43±0.16) was up-regulated in IL-17A stimulated group ( t=19.92, P=0.006; t=21.04, P=0.007) were up-regulated and Bcl-2, Bcl-XL mRNA expression (0.48±0.03, 0.83±0.10) were down-regulated in the IL-17A inhibition group ( t=29.44, P=0.027; t=16.31, P=0.023). The results of protein blotting assay showed that, Beclin-1 and LC3 protein expression (0.51±0.10, 0.559±0.010) were decreased in IL-17A stimulated group compared with Beclin-1, LC3 protein expression (0.72±0.09, 0.635±0.017) in PBMCs group ( t=14.38, P=0.034; t=17.99, P=0.014); BecLin-1 and LC3 protein expression (0.83±0.11, 0.737±0.025) increased in the IL-17A inhibition group ( t=9.72, P=0.027; t=22.35, P=0.007). Conclusion:IL-17A plays a role in pSS by regulating the expression of inflammatory factors IL-4, IFN-γ, IL-13 and autophagy related genes Beclin1 and LC3.

Atopic dermatitis-like lesions appearing after interleukin-17 antagonist therapy in 4 cases of psoriasis: case analysis and literature review / 中华皮肤科杂志

Objective:To summarize and analyze clinical characteristics and possible pathogenesis of atopic dermatitis (AD) -like lesions after treatment with interleukin-17 (IL-17) antagonists in patients with psoriasis, so as to improve the clinical management of these patients.Methods:Four patients with psoriasis, who developed AD-like lesions after the treatment with IL-17 antagonists, were reported. A comprehensive update-search was carried out to analyze and summarize clinical characteristics of and therapeutic strategies for other related cases reported in Chinese and international literature.Results:Among the 4 patients in this study, 2 were males and 2 were females, with a history of psoriasis ranging from 10 to 35 years; after 5-month to 2-year treatment with secukinumab, they developed pruritic erythema and papules with exudation on the trunk, limbs and/or face. All the 4 patients had a history of atopic diseases and elevated serum total IgE levels and/or eosinophil counts. AD-like lesions were controlled in 3 patients after treatment with systemic cyclosporine, glucocorticoids and/or antihistamines, as well as topical glucocorticoids and/or tacrolimus, and secukinumab continued to be administered simultaneously; 1 discontinued secukinumab due to repeated AD-like lesions. Totally, 12 articles in English containing 48 patients were included, and a total of 52 patients including the 4 patients in this study were analyzed. Among them, there were 30 males and 22 females, with the age being 50.1 ± 13.6 years; 37 cases were induced by secukinumab, 14 induced by ixekizumab, and 1 induced by brodalumab; the time from the initiation of biologic therapy to the onset of AD-like lesions ranged from 1 week to 2 years; the lesions manifested as pruritic erythema and papules, accompanied by scales or exudation; the skin lesions were mainly distributed on the limbs (41 cases, 78.8%), followed by the trunk (32 cases, 61.5%) and face (20 cases, 38.5%) ; a personal or family history of atopic diseases was reported in 57.7% patients; peripheral blood eosinophil counts increased in 5 cases, and serum total IgE levels were elevated in 17. Thirty-two (61.5%) patients discontinued IL-17 antagonists, and received single or combination therapies, including systemic treatment with cyclosporine, methotrexate, glucocorticoids, antihistamines, other biologic agents and small-molecule drugs, topical treatment with glucocorticoids and/or tacrolimus, and phototherapy; 20 (38.5%) patients continued the previous treatment with IL-17 antagonists, and additionally received topical treatment with or without oral antihistamines or cyclosporine; after the above treatment, the psoriatic and AD-like lesions were controlled in most patients.Conclusions:AD-like lesions after IL-17 antagonist therapy were not common in patients with psoriasis, and these patients developing AD-like lesions were more likely to have a personal or family history of atopic diseases and elevated levels of serum total IgE; based on the disease condition, the treatment with IL-17 antagonists may be considered to continue during the symptomatic treatment of AD-like lesions.

S100A10 protein expression in psoriatic lesions and its effect on psoriasis-like skin inflammation in mouse models / 中华皮肤科杂志

Objective:To determine S100A10 protein expression in psoriatic lesions, and to investigate its effect on psoriasis-like skin inflammation in imiquimod (IMQ) -induced mouse models.Methods:From January 2020 to June 2022, skin lesions were surgically collected from 28 patients with psoriasis in the Department of Dermatology, the First Affiliated Hospital of Xinxiang Medical University; normal skin tissues were collected from 18 healthy subjects in the Department of General Surgery and Department of Ophthalmology during the same period, and served as a control group. Immunohistochemical staining was performed to determine the S100A10 protein expression in skin lesions from psoriasis patients and normal skin tissues from healthy controls. Ten wild-type (WT) C57BL/6J female mice and 10 S100A10 -/- C57BL/6J female mice were selected to establish the IMQ-induced mouse models of psoriasis-like skin inflammation. Then, the mice were randomly divided into gene knock-out (KO) /IMQ group, WT/IMQ group, KO/vaseline (VAS) group, and WT/VAS group by using a random number table, and there were 5 mice in each group. The mice in the KO/IMQ group and WT/IMQ group were topically treated with IMQ cream (62.5 mg) on the shaved back daily to establish the mouse models of psoriasis-like skin inflammation, while the mice in the KO/VAS group and WT/VAS group were topically treated with vaseline cream (62.5 mg) daily, and both treatments lasted 7 consecutive days. Skin lesions on the back were observed daily. On day 7, the mice were sacrificed by cervical dislocation, and their dorsal skin tissues were excised. The IMQ-induced psoriasis-like skin inflammation was evaluated by the psoriasis area and severity index (PASI), pathological manifestations of skin lesions were observed by hematoxylin and eosin staining, the expression of S100A10 and Ki-67 in skin lesions was determined by immunohistochemical staining, the expression of STAT3, IL-17A and other cytokines was determined by Western blot analysis, and IL-17 mRNA expression was determined by real-time fluorescence-based quantitative PCR (qPCR). Statistical analysis was carried out by using the independent sample t-test, nonparametric U test, and chi-square test. Results:Immunohistochemical staining showed that the S100A10 protein expression was significantly lower in the psoriasis vulgaris lesions than in the normal control skin tissues ( Z = -3.47, P < 0.001). In the mouse models, the S100A10 protein expression was significantly lower in the skin lesions of mice in the WT/IMQ group than in the skin tissues of mice in the WT/VAS group ( t = 3.64, P = 0.007), and the Ki-67 expression was significantly higher in the KO/IMQ group than in the WT/IMQ group ( t = 2.97, P = 0.041). Additionally, the mice in the KO/IMQ group presented with more severe clinical manifestations such as scales and infiltration compared with those in the WT/IMQ group. Western blot analysis showed that the phosphorylated STAT3/STAT3 expression and IL-17A protein expression was significantly higher in the KO/IMQ group than in the WT/IMQ group ( t = 3.27, 3.48, P = 0.031, 0.025, respectively), and qPCR revealed that the IL-17A mRNA expression was also significantly higher in the KO/IMQ group than in the WT/IMQ group ( t = 2.73, P = 0.029) . Conclusion:S100A10 protein was underexpressed in the skin lesions of psoriasis patients, and the deletion of S100A10 protein aggravated IMQ-induced psoriasis-like skin inflammation in mice, possibly by upregulating STAT3 phosphorylation in the epidermis.

Biological agents targeting interleukin-23/Th17 axis in inflammatory skin diseases: from basic research to clinical application / 中华皮肤科杂志

Interleukin-17 (IL-17) has been proved to be closely associated with the pathogenesis of various inflammatory skin diseases. Its main source is Th17 cells, whose differentiation is evoked by interleukin-23 (IL-23). Therefore, the IL-23/Th17 axis is an emerging target for the treatment of inflammatory skin diseases. IL-17 antagonists, IL-23 antagonists and IL-12/23 antagonists have shown satisfactory efficacy and safety in the treatment of psoriasis, atopic dermatitis, hidradenitis suppurativa, pityriasis rubra pilaris and SAPHO syndrome in latest clinical trials. Accordingly, this review mainly summarizes progress in molecular signaling pathways in and pathophysiological basis of the IL-23/Th17 axis in the occurrence of inflammatory skin diseases, as well as clinical application of different biological agents targeting this axis.

The Key Role of Interleukin-17A/Interleukin-17RA in Bone Metabolism and Diseases: A Review

@#Bone metabolism requires a balance mechanism between intricate processes of bone formation and resorption, which is affected by the essential interaction between osteoblasts and osteoclasts. Interleukin-17 (IL-17) is a family of cytokines consisting of six isoforms: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F. Among these isoforms, IL-17A has shown promising and novel roles in the regulation of bone metabolism. IL-17A has also captivated the interest of many researchers since its discovery because of its role as a pro-inflammatory cytokine which mediates a few inflammatory processes. This review describes the biology of IL-17A and its receptor as well as summarises the regulatory role of IL-17A in bone metabolism and diseases through some known pathways. Understanding the function of IL-17A in bone metabolism may lead to the development of therapeutics or diagnostic strategies for some bone diseases; as well as future therapy using tissue engineering and regenerative medicine approaches.

Expression of serum IL-17A,S100A8 and S100A9 in children with severe Mycoplasma pneumoniae pneumonia and its significance in prognosis / 国际检验医学杂志

Objective To study the expression of serum interleukin(IL)-17A,calcium binding protein S100A8 and S100A9 in children with severe Mycoplasma pneumoniae pneumonia(SMPP)and their prognostic significance.Methods A total of 116 children with SMPP who were diagnosed and treated in this hospital from March 2019 to March 2021 were enrolled as the SMPP group.According to the pediatric critical cases score,the SMPP children divided into non-critical group(43 cases),critial group(40 cases),extremely critical group(33 cases).According to the prognosis of 28 d after admission,the SMPP children were divided into a good prognosis group with 82 children and a poor prognosis group with 34 children.A total of 60 physical ex-amination of healthy children in the same hospital during the same period were enrolled as the control group.The levels of serum IL-17A,S100A8,S100A9,procalcitonin(PCT),C-reactive protein(CRP),IL-6 and tumor necrosis factor(TNF)-α were detected in each group.Pearson correlation analysis was used to analyze the cor-relation between serum levels of IL-17A,S100A8,S100A9 and PCT,CRP,IL-6,and TNF-α.Multivariate Lo-gistic regression analysis was used to analyze the factors affecting the poor prognosis of children with SMPP.The receiver operating characteristic(ROC)curve was used to analyze the value of each index in predicting the poor prognosis of children with SMPP.Results The SMPP group had significantly higher serum levels of IL-17A,S100A8,S100A9,PCT,CRP,IL-6,and TNF-α than the control group(P<0.05).In children with SMPP,the serum levels of IL-17A,S100A8,and S100A9 were positively correlated with PCT,CRP,IL-6,and TNF-α(P<0.05).The serum levels of IL-17A,S100A8 and S100A9 in extremely critical group were signifi-cantly higher than those in critical group and non-critical group(P<0.05).Elevated serum levels of IL-17A,S100A8 and S100A9 were independent risk factors for poor prognosis in children with SMPP.The area under the curve(AUC)of combined detection of serum IL-17A,S100A8 and S100A9 for predicting poor prognosis in children with SMPP was 0.895,which was higher than that of single detection of serum IL-17A,S100A8 and S100A9(0.833,0.764,0.810),the differences were all statistically significant(Z=3.780,6.723,5.012,P<0.059).The sensitivity and specificity of combined detection were 0.891 and 0.755,respectively.Conclu-sion The serum levels of IL-17A,S100A8 and S100A9 are increased in children with SMPP,which are related to the severity of SMPP.The combined detection of the three indicators has a high predictive value for the poor prognosis of SMPP.

Research progress on the roles and mechanisms of γδT cells in periodontitis / 口腔疾病防治

@#Periodontitis is a chronic infectious disease that occurs in periodontal support tissues. Plaque microorganisms are its initiating factor, while local inflammation and alveolar bone loss resulting from periodontitis are the most common causes of tooth loss. Interleukin-17 (IL-17), which plays an important role in the immune response to periodontitis, mostly originates from T helper cell 17 (Th17) and γδT cells. In periodontitis, the role of Th17 cells has been demonstrated broadly, but the role of γδT cells was not revealed until recent years. As a highly heterogeneous group of T lymphocytes, γδT cells are considered a link between innate immunity and adaptive immunity. Studies have found that γδT cells are mostly distributed in the oral epithelium near the biofilm, where they can interact with microorganisms to produce IL-17, recruit neutrophils, macrophages, etc., and participate in the host immune response to periodontitis. They also play a role in the association between periodontitis and relevant systemic diseases. In addition, γδT cells have been proven to produce tissue repair-related factors with a protective effect against periodontitis. The possible mechanism of γδT cells in periodontitis is discussed in this review.

Serum B7 homologous protein 2, tumor necrosis factor-related apoptosis-inducing ligand, interleukin-37, interleukin-17A levels in patients with primary immune thrombocytopenia and their clinical significance / 中国医师进修杂志

Objective:To explore the changes of serum B7 homolog 2 (B7-H2), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interleukin(IL)-37 and IL-17A levels in patients with primary immune thrombocytopenia (ITP), and to analyze the clinical guiding significance of each index level in the diagnosis and treatment of ITP.Methods:A total of 90 patients with ITP treated in Jining Hospital of Traditional Chinese Medicine from September 2018 to September 2020 were retrospectively selected as the research group, and 90 healthy patients during the same period were selected as the normal control group. The levels of serum B7-H2, TRAIL, IL-37, IL-17A and platelet count (PLT) in the two groups were compared, and the clinical guidance significance of each index level in the diagnosis and treatment of ITP were analyzed by receiver operating characteristic(ROC) curve.Results:The serum levels of B7-H2, TRAIL, IL-37 and IL-17A in the research group were higher than those in the normal control group, and PLT was lower than that in the normal control group: (25.12 ± 4.29) μg/L vs. (12.26 ± 3.10) μg/L, (0.92 ± 0.20) μg/L vs.(0.46 ± 0.13) μg/L, (145.02 ± 43.18) ng/L vs. (50.23 ± 14.07) ng/L, (21.63 ± 5.06) ng/L vs. (7.71 ± 2.04) ng/L, (16.12 ± 4.61) × 10 9/L vs. (200.86 ± 61.4) × 10 9/L, there were statistical differences ( P<0.05). After treatment for 3 months, 73 patients obtained remission, and 13 patients were non-remission. The levels of B7-H2, TRAIL, IL-37, IL-17A in the non-remission group before and after treatment were higher than those in the remission group, and PLT was lower than that in the remission group, there were statistical differences ( P<0.05). Pearson correlation analysis showed that the levels of serum B7-H2, TRAIL, IL-37 and IL-17A were negatively correlated with PLT ( P<0.05). The ROC curve analysis showed that the area under the curve of serum B7-H2, TRAIL, IL-37 and IL-17A in prognostic prediction was 0.916, the sensitivity and the specificity were 94.12% and 86.30%. Conclusions:The serum levels of B7-H2, TRAIL, IL-37 and IL-17A in patients with ITP are significantly elevated, and are closely related to the level of PLT. Combined detection can help clinically predict the direction of disease outcome.

Efficacy of probiotics, mesalazine and Kangfuxin liquid in combination in the treatment of 53 cases of ulcerative colitis / 中国基层医药

Objective:To investigate the efficacy of probiotics, mesalazine and Kangfuxin liquid in combination on ulcerative colitis and its effects on inflammatory factors. Methods:A total of 106 patients with ulcerative colitis admitted to Zhejiang Sian International Hospital from November 2021 to May 2022 were included in this study. They were randomly assigned to receive treatment with either probiotics, mesalazine and Kangfuxin liquid in combination (combined therapy group, n = 53) or mesalazine alone (monotherapy group, n = 53) for 30 days. Clinical efficacy, inflammatory factor level and Rachmilewitz endoscopic score pre- and post-treatment as well as the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the combined therapy group was significantly higher than that in the monotherapy group [98.1% (52/53) vs. 79.3% (42/53), χ2 = 9.40, P < 0.05]. After treatment, tumor necrosis factor-a, interleukin-8, and interleukin-17 levels were significantly decreased, and interleukin-10 level was significantly increased (all P < 0.05). Tumor necrosis factor-a, interleukin-8, and interleukin-17 levels as well as Rachmilewitz endoscopic score in the combined therapy group were significantly lower than those in the monotherapy group ( t = -2.22, -5.85, -14.08, -2.62, all P < 0.05). The interleukin-10 level in the combined therapy group was significantly higher than that in the monotherapy group ( t = 3.91, P < 0.05). The incidence of clinical symptoms in the combined therapy group was significantly lower than that in the monotherapy group [11.3% (6/53) vs. 54.7% (29/53), χ2 = 22.57, P < 0.001]. There was no significant difference in the incidence of adverse reactions between the two groups ( P = 0.540). Conclusion:Probiotics, mesalazine and Kangfuxin liquid in combination for the treatment of ulcerative colitis can improve clinical efficacy, decrease inflammatory factor levels, reduce clinical symptoms, and have a few adverse reactions.

Interleukin-17 and interleukin-23 inhibitors in the treatment of pustular psoriasis / 中华皮肤科杂志

Pustular psoriasis is a serious life-threatening disease, and patients usually show poor response to traditional treatments. In recent years, interleukin-17 and interleukin-23 inhibitors have shown favorable efficacy in the treatment of psoriasis. This review summarizes the latest progress in interleukin-17 and interleukin-23 inhibitors for the treatment of pustular psoriasis.