| Objective: The imbalance of Th1/Th2 has relation to the pathogenesis of many autoimmune diseases. There are many researches about the imbalance of Th1/Th2 in Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Ankylosing spondylitis (AS) is considered as an immune- associated chronic inflammatory disease, whether the imbalance of Th1/Th2 takes part in its pathogenesis is poorly understood. The aim of our study is to investigate the patterns of helper T cells (Th) in the peripheral blood and the levels of TNF-αand IL-10 in the serum and synovial fluid to understand the role of the imbalance of Th1/Th2 and Th1/Th2 cytokines in the pathogenesis of AS.Methods: 50 patients including 30 subjects with AS and 20 subjects with RA and 20 normal controls had been chosen. All the patients never took DMARDs and biological agents. Serum was taken from all the patients and normal controls, synovial fluid was taken from patients with AS. The onset locations and detections of sacroiliitis by computed tomography(CT) of patients with AS were recorded. Blood was taken for determination of HLA-B27, ESR, CRP and so on. Enzyme linked immunosorbent assay (ELISA) was used to measure the levels of TNF-αand IL-10 in the serum and synovial fluid. The levels of TNF-αand IL-10 in the serum and synovial fluid were made statistical analysis, correlation coefficients and significances were calculated between TNF-α(or IL-10) and laboratory parameters of disease activity (ESR, CRP). Three-color flow cytometric analysis was employed for surface antigens (CD3, CD4) of Th cells and intracellular cytokines (IFN-γ/IL-4) of Th1/Th2 in the peripheral blood of patients with AS and normal controls.SAS8.0 was used to analyse all data. Quantitative data were expressed as ( x±s). P value <0.05 was considered significant.Results: 1 The demographic details: In the group of 30 patients with AS, every patients had peripheral arthritis, the mean disease duration was (10.93±5.07) months, with a mean age of (26.00±3.69) yr, 17 subjects were male, 13 subjects were female, 27 subjects were HLA-B27 positive, 3 subjects were HLA-B27 negative. In 20 normal controls, with a mean age of (25.15±3.79) yr, 12 subjects were male, 8 subjects were female. In the group of 20 patients with RA, with a mean age of (26.75±3.51) yr, 12 subjects were male, 8 subjects were female, the mean disease duration was (8.53±3.28) months. There were no differences between the patients and normal controls in age, gender (P>0.05). In the group of 30 patients with AS, ESR (69.63±16.85) mm/60min, CRP (77.10±19.40) mg/l, according to the detections of sacroiliitis by CT scan, 20 subjects with sacroiliitis displayed grade II bilateral, 6 subjects displayed grade III bilateral, 3 subjects displayed grade III unilateral, 1 subjects displayed grade IV unilateral.2 The serum levels of TNF-αand IL-10 in different groups: TNF-αand IL-10 serum levels were (16.05±2.01) ng/L and (5.88±1.02) ng/L in patients with AS, (19.19±1.49) ng/L and (4.89±1.07) ng/L in patients with RA, significantly higher than in normal controls [(4.80±1.43) ng/L and (2.47±0.77) ng/L (P<0.05)]; The serum level of TNF-αwas significantly higher in patients with RA than in patients with AS (P<0.05),The serum level of IL-10 was significantly higher in patients with AS than in patients with RA (P<0.05); The rate of TNF-α/IL-10 was significantly higher in patients with AS (2.81±0.59) than in normal controls (2.02±0.64) (P<0.05), but it was significantly lower than in patients with RA (4.08±0.82) (P<0.05).3 The synovial fluid levels of TNF-αand IL-10 in patients with AS: The synovial fluid level of TNF-α(26.55±2.29) ng/L was significantly higher than the serum level (P<0.05); The synovial fluid level of IL-10 was (5.83±1.32) ng/L, it was not significantly different from the serum level (P>0.05).4 The rate of Th1/Th2 in the peripheral blood and the production of Th1/Th2 intracellular cytokines (IFN-γ, IL-4): In patients with AS, the percentage of CD3+CD4+T cells in the peripheral blood was (33.65±5.62)%, there was no significant difference compared with normal controls (35.10±4.29)% (P>0.05); The percentage of intracellular cytokine of Th1 (IFN-γ) in patients with AS was (1.98±0.17)%, which was significantly higher than in normal controls (0.48±0.07)% (P<0.05); The percentage of intracellular cytokine of Th2 (IL-4) in patients with AS was (1.09±0.20)%, which didn't have significant difference compared with normal controls (1.11±0.21)% (P>0.05); In patients with AS, the rate of Th1/Th2 in the peripheral blood was (1.81±0.30), which was significantly higher than in normal controls (0.45±0.09) (P<0.05).5 The Correlation between the serum level of TNF-α(or IL-10) and laboratory parameters of disease activity (ESR, CRP): According to correlation analysis, the serum level of TNF-αcorrelated significiently with ESR, CRP (r=0.54,0.44, P<0.05); There wasn't significant correlation between the serum level of IL-10 and ESR, CRP (P>0.05); There wasn't significant correlation between the rate of TNF-α/IL-10 and ESR, CRP (P>0.05).6 The Correlation between the percentage of Th cells in the peripheral blood (or the proporationality of Th1/Th2) and laboratory parameters of disease activity (ESR, CRP): According to correlation analysis, the percentage of Th1 cells (or Th2 cells) and the proporationality of Th1/Th2 didn't have significant correlation with laboratory parameters of disease activity (ESR, CRP) (P>0.05).7 The serum level of TNF-αcorrelated significiently with the percentage of Th1 cells in the peripheral blood (r=0.43, P<0.05). The serum level of IL-10 didn't have significient correlation with the percentage of Th2 cells in the peripheral blood (P>0.05).Conclusion: 1 The serum levels of TNF-αand IL-10 increased significantly in patients with AS, and even more obvious of TNF-α. It suggests that TNF-αas an inflammatory factor plays an important part in the pathogenesis of AS, IL-10 could inhibit the production of TNF-α, the increase of the serum level of IL-10 may be compensated, but it isn't enough. Imbalance exists in Th1/Th2 cytokine network, there is a strong predominance of Th1.2 There was higher level of TNF-αin the synovial fluid than in the serum, it suggests that TNF-αmay have relation to the pathological changes of the synovium in the peripheral joints and articular cartilage destructions.3 There was not significant difference of the percentage of Th cells in the peripheral blood between patients with AS and normal controls, the percentage of intracellular cytokine of Th1 (IFN-γ) increased, but not the Th2 (IL-4). It suggests that there is an imbalance in Th1/Th2 in the peripheral blood of patients with AS, and towards Th1, the imbalance of Th1/Th2 may plays a part in the pathogenesis of AS.4 The serum level of TNF-αsignificantly increased, and had correlation with laboratory parameters of disease activity (ESR, CRP), that could provide reference to the monitoring of pathogenetic conditions of patients with AS.5 The test of serum cytokine network may provide theory evidence to the use of biological agents for AS and the development of new drugs.
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