Differential Th1/Th2 cytokine patterns in chronic arthritis: interferon gamma is highly expressed in synovium of rheumatoid arthritis compared with seronegative spondyloarthropathies

Objective-To investigate possible differences in Th1 and Th2 cytokine mRNA expression in the synovial tissue (ST) of patients with rheumatoid arthriti s (RA) and seronegative spondyloarthropathies (SpA) with diagnostic and/or pathogenic interest. Methods-Eleven RA patients and 14 SpA patients (10 with undifferentiated sp ondyloarthropathy (USpA), two with ankylosing spondylitis (AS) and two with psoriatic arthritis (PsA)) were included. Th1 (interferon gamma, interleuk in 2) and Th2 (interleukin 4, interleukin 5 and interleukin 10) cytokine mR NA levels from arthritic knee ST were quantified by using an optimised poly merase chain reaction method with a computerised analysis system. Protein l evels of proinflammatory cytokines (interleukin 1, tumour necrosis factor a lpha and interleukin 6) in synovial fluid were quantified with a specific E LISA test. Results-Th1 cytokines were detected in all of RA ST samples in contrast wit h 58% (interferon gamma) and 71% (interleukin 2) of SpA samples. Th2 cytoki nes were expressed in 90% of RA ST samples, but the findings in SpA were in terleukin 10 in 90%, interleukin 4 in 60% and interleukin 5 in 40% of ST sa mples. However, when the mRNA levels of each cytokine were quantified and c orrected for T cell mRNA levels, only interferon gamma levels were signific antly higher in RA than in SpA (p<0.003). Thus, the Th1/Th2 cytokine ratio in RA Spain was fivefold that of SpA. Synovial fluid interleukin 1 beta con centrations were higher in RA than in SpA (p<0.05); there were also higher synovial fluid levels of tumour necrosis factor alpha in RA than in SpA, bu t without statistical significance. Conclusion-This study has detected both Th1 and Th2 cytokine gene expressio n in ST from RA and SpA patients. Synovium interferon gamma mRNA levels and SF interleukin 1 beta protein levels were significantly higher in RA than in SpA, so reflecting the known proinflammatory activity of interferon gamm a through macrophage activation. Thus, the Th1 (interferon gamma)/Th2 (inte rleukin 4) ratio is significantly higher in RA than in SpA ST. These data c onfirm previous studies on ST Th1/Th2 balance in RA and extend previous wor k in comparing ST RA with subgroups of SpA distinct of ReA.