Significance Of Th17Cells And Related Cytokines IL-17, IL-6and IL-23on Rheumatoid Arthritis

Objective: Rheumatoid arthritis (RA) is a kind of chronic systemicautoimmune disease with the joints inflammation. Until now, the pathogenicmechanism of RA is still unclear. A lot of data has suggested that autoimmuneresponse and associated cytokines contribute to the pathogenesis in RA. CD4+T cells (Th) are essential regulators of immune responses and inflammatorydiseases. Interleukin17(IL-17)-producing T helper cells (Th17) are a newsubset of T helper cells. The primary cytokine of Th17cells, IL-17, exertspotent proinflammatory and joint-destructive activities. Many cytokinesregulate the differentiation of Th17cells, IL-6induces Th17celldifferentiation in vivo, IL-23participates in the generation of Th17cells. Theinduction effect of Th17cells and related cytokines IL-17, IL-6and IL-23inRA is extremely important. The aim of this study was to assess the role ofTh17cells and related cytokines in RA by investigating the percentage ofTh17cells in Peripheral blood and the levels of related cytokines IL-17, IL-6and IL-23in serum.Methods: Thirty RA patients were chosen. All patients were previouslyuntreated. Glucocorticoid (GC), disease modifying antirheumatic drugs(DMARDs) and biologic agent were never used for the RA patients. Theclassification of all RA patients were consistent with American RheumatismInstitute and European congress prevention federation rheumatoid arthritisdiagnostic criteria of2009. Twenty healthy people as control were chosen.Serum was taken from all the patients and normal controls. Clinic indexes ofpatients with rheumatoid arthritis were recorded such as age, disease duration,symptoms, the number of joint tenderness and swelling, DAS28, RF, ESR,CRP, etc. Avidin biotin peroxidase complex enzyme-linked immunosorbentassay (ABC-ELISA) was used to measure the serum levels of IL-17,IL-6and IL-23, which were compared between RA and normal group. The correlationcoefficients and significances were calculated between the related cytokines ofTh17cells and the laboratory parameters (ESR, CRP, RF, DAS28). Flowcytometric analysis (FCM) was employed for detecting the percentage ofperipheral blood Th17cells in RA, which were compared between RA andnormal group. The correlation coefficients and significances were calculatedbetween the percentage of Th17cells and the laboratory parameters (ESR,CRP, RF, DAS28).All the data were analyzed by statistical software SPSS17.0for windows.The mean number±standard deviation (x±s) was used to express themeasurement data. The test was adopted for comparison between groups.Chi-square test was used for the comparison of the enumeration data. Linearcorrelation analysis was performed for correlationship. P value<0.05wasconsidered significant.Results:1The demographic details and traditional parameters of disease activity in RA:In the group of30patients with RA, the course of the disease was from1month to20years, with median duration of42months. The mean age was(50.23±10.85) yr, and10subjects were male,20subjects were female. In20normal controls, with a mean age of (46.90±5.38) yr,6subjects were male,14subjects were female. There were no differences between the patients andnormal subjects in age, gender (P>0.05). In the group of30patients with RA,the average ESR, CRP and DAS28were (73.50±28.54)mm/h,(54.12±37.18)mg/L,(6.53±1.21); RF was283.50(360.25)IU/ml.2IL-17, IL-6and IL-23levels in serum of RA patients: The serum levels ofIL-17, IL-6and IL-23in RA patients were(7.96±3.06)ng/L,(3.72±1.53)ng/L and (1019.15±291.57)ng/L, which were significantly higher thannormal group (2.51±0.40)ng/L,(1.23±0.15)ng/L and (289.45±43.72)ng/L. There were significant differences between RA group and normal group(P<0.01).3The percentage of peripheral blood Th17cells in RA: The percentage of peripheral blood Th17cells in RA was (2.35±1.03)％,which weresignificantly higher than normal group(0.66±0.26)％(P<0.01).4The correlation between serum levels of the IL-17,IL-6,IL-23and activityindex of disease (ESR, CRP, RF, DAS28): According to correlation analysis,the level of IL-17in serum had significant positive correlation with ESR,CRPand DAS28(r=0.569,0.632,0.593,P＜0.01); the level of IL-6in serum hadsignificant positive correlation with ESR,CRP and DAS28(r=0.585,0.575,0.649,P＜0.01); There was no correlation between the level of IL-23in serumand ESR,CRP and DAS28(P>0.05); none of IL-17,IL-6and IL-23hadcorrelation with RF (P>0.05).5The correlation between the percentage of peripheral blood Th17cells in RAand the laboratory parameters of disease activity: According to correlationanalysis, The percentage of peripheral blood Th17cells in RA had significantpositive correlation with ESR,CRP and DAS28(r=0.561,0.586,0.574,P＜0.01); there was no significant correlation between the percentage ofperipheral blood Th17cells in RA and RF (P>0.05).6The correlation between serum levels of the IL-17,IL-6,IL-23and thepercentage of peripheral blood Th17cells: the percentage of peripheral bloodTh17cells in RA had significant positive correlation with serum level of IL-17(r=0.528,P＜0.01); the percentage of peripheral blood Th17cells in RA hadpositive correlation with serum level of IL-6(r=0.404,P＜0.05), but had nocorrelation with IL-23(P＞0.05); the serum level of IL-17had positivecorrelation with serum level of IL-6(r=0.397, P＜0.05),but had no correlationwith IL-23(P＞0.05). there was no correlation between serum level of the IL-6and IL-23(P＞0.05).Conclusions:1The serum levels of IL-17and IL-6significantly increased in patients withRA, IL-17and IL-6had positive correlation with laboratory parameters ofdisease activity, which could provide a disease activity index for monitoringRA disease.2The serum level of IL-23significantly increased in patients with RA, IL-23 had no correlation with laboratory parameters of disease activity, which couldprovide that IL-23participates in the pathogenesis of RA,but not accompanieswith disease activity of RA.3The percentage of peripheral blood Th17cells in RA group was significantlyhigher than in normal controls group and it had correlation with laboratoryparameters of disease activity. Th17cells might play a role in the pathogenesisof RA and had a relationship with the development of RA.4There was positive correlation between the percentage of peripheral bloodTh17cells and serum levels of IL-17,IL-6in RA, which indicated that thethree increasing index may imply some causal relationship. the percentage ofperipheral blood Th17cells and serum levels of IL-17,IL-6may have closecorrelation with the state of RA patients in the development of RA, which washelpful for observing the patient's condition.5The serum level of IL-23had no correlation with the percentage ofperipheral blood Th17cells and serum levels of IL-17,IL-6, which indicatedthat IL-23did not participate in the generation of Th17cells.6Th17cells and related cytokines IL-17, IL-6and IL-23play an importantrole in the development of RA.