The Role Of IL-17, IL-4 And Tc1/Tc2 Imbalance In Ankylosing Spondylitis

Objective: Ankylosing Spondylitis is a kind of chronic and progressive inflammatory disease,whose pathogenesy is very complex.Although it is thought that the disease is correlated to immunity,infection and genetic factor HLA-B27 at present,the etiopathogenisis is not yet identified completely up to now.The study found that they played an vitally important role in the pathogenesis of AS,which are CD4+T helper cell (Th cell),CD8+T cytotoxic cell (Tc cell) and cytokine.The Th cells are divided into Th1 and Th2 subgroup and the Tc cells are divided into Tc1 and Tc2 subgroup according to the cytokine excreted by them. IL-17,excreted by Th1 and Tc1 cells,is the early starting factor of the inflammatory reaction induced by T cell.The function of IL-4,excreted by Th2 and Tc2 cell,is to inhibit cell immunity and promote humoral immunity.Some data shows that the morbility criticality of AS may be activation of Tc cell,even not with participation of Th cell.Its correctness is sufficiently proved by the finding of study that AS can still happen if the CD4 gene of the mouse was removed.The T lympholeukocyte of abnormal activation educes pathogenesis by excreting different cytokine.It is confirmed that there are Tc cells which can identify germ and autoantibody in inside of joint of AS patients.Some authors think the imbalance of Tc1/Tc2 is the criticality leading to AS,but the report is rare about this aspect.Therefore,through detecting the level of IL-17 and IL-4 in the serum and synovial fluid of AS patients and the Tc1/Tc2 imbalance in peripheral blood in our study,we study the change of cytokine network and the role of Tc1/Tc2 imbalance in the pathogenesy of AS and provide some theoretical evidence for the choose of clinical treatment plan.Methods: Thirty untreatly AS patients,twenty untreatly RA patients that never take medicine of MTX,SASP and biologic agent and twenty healthy controls were chosen.AS patients was consistent with New York criteria revised in 1984 and RA patients was consistent with American Rheumatology Academy rheumatoid arthritis diagnostic ceiteria of 1987;The ESR,CRP and clinical symptoms of AS patients are recorded.The serum of AS patients,RA patients and healthy controls and synovial fluid of AS patients are kept and conserved in -80℃refrigerator.The level of IL-17 and IL-4 in serum and synovial fluid samples were test with a double-antibody enzymelinkedimmunosorbent assay(ELISA).The blood with heparin sodium anticoagulation of AS patients and healthy controls are test with flow cytometry each samples of CD3+CD8+ T lympho-cyte phaenotype,the Tc1 type cytokine IFN-γof intracytopl-asm and the Tc2 type cytokine IL-4 of intracytoplasm.Corr-elation coefficients and significant were calculated between IL-17(or IL-4),Tc1 cells,Tc2 cells,Tc1/Tc2 and traditional parameters of disease activity(ESR and CRP).SAS8.0 was used to process all data. Quantitative data were expressed as ( x±s).Two samples mean comparation t test was used to in two groups and linear correlation was used to in correlation. P values of <0.05 were considered significant.Results: 1 The level of IL-17 in serum of AS patients (16.46±8.62)ng/L was obviously higher than healthy control group(9.51±2.97)ng/L(P<0.05);The levels of IL-4 in serum of AS patients(6.94±4.13) ng/L was obviously lower than healthy control group(17.81±4.69)ng/L(P<0.05).The level of IL-17 in serum of RA patients(15.01±4.38)ng/L was obviously higher than healthy control group(9.51±2.97)ng/L(P<0.05);The level of IL-4 of serum was no significant differece between RA patients(21.91±13.25)ng/L and healthy control(17.81±4.69) ng/L(P>0.05).The level of IL-17 in serum was no significant differece between the AS and the RA(P>0.05).The level of IL-4 in serum of AS was obviously higher than RA(P<0.05).2 The level of IL-17 in synovial fluid of AS patients (32.6±9.97)ng/L was obviously higher than serum (16.46±8.62) ng/L (P<0.05);The level of IL-4 in synovial fluid of AS patients (17.70±6.55)ng/L was obviously lower than serum (6.94±4.13)ng/L (P<0.05).3 The percentage of CD3+CD8+T cells in peripheral blood of AS patients(23.74±6.81)% was obviously higher than healthy controls(17.55±3.89)% (P<0.05).The percentage of Tc1 cells in peripheral blood of AS patients(0.38±0.38)% was obviously lower than healthy controls(1.58±1.57)%(P<0.05).The percentage of peripheral blood Tc2 cells in patients with AS(0.59±0.61)% was no significant differece with healthy controls(0.46±0.28)%(P>0.05).The ratios of Tc1/Tc2 in AS patients(0.77±2.01) was obviously lower than healthy controls (4.07±3.88)(P<0.05).4 There was no significant correlation between the levelof IL-17 in serum of AS patients and ESR,CRP(r=-0.3857,0.1317, P>0.05).There was significant inverse correlation between IL-4 and ESR(r=-646467,P<0.01) and There was no significant correlation between IL-4 and CRP(r=0.2797, P>0.05).There was no significant correlation between Tc1, Tc2, Tc1/Tc2 and inflammatory index(ESR and CRP).(r=-0.0717,-0.2396,0.1223,-0.3312,-0.0549,-0.2358,P>0.05).Conclusion: 1 The disorder of immune function existed really in the AS patients.The level of IL-17 promoting the development of inflamation in secrum increased obviously and the level of IL-4 inhabiting the inflammatory reaction cut down notably, therefore,it is demonstrated that the change of the two CKs'level plays a critical role in the morbility of AS.In the serum of RA patients,high level of IL-17 also exists.It is proved that there is close relationship between the IL-17 and the RA.2 There were high level of IL-17 and IL-4 in synovial fluid of AS,where were more than that in serum of AS.It indicates that IL-17 and IL-4 have the tendency of moving and gathering to joint and there is close relationship between them and synovium affection,destruction of bone in AS.3 In peripheral blood of AS patients,Tc1 cells decreasing, Tc2 cells no obviously changing,and the Tc1/Tc2 imbalance existed and Tc2 cells prevailed.4 There is inverse correlation between the level of IL-4 in serum of AS patients and ESR,thus the ability of restraining infammatory reaction decreased and the ESR of inflamation index steped up accompanying the degrading of IL-4.It is proved that there is close relationship between the IL-4 and the activity of pathogenetic condition in AS.