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

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Abstract
OBJECTIVE To investigate possible differences in Th1 and Th2 cytokine mRNA expression in the synovial tissue (ST) of patients with rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA) with diagnostic and/or pathogenic interest. METHODS Eleven RA patients and 14 SpA patients (10 with undifferentiated spondyloarthropathy (USpA), two with ankylosing spondylitis (AS) and two with psoriatic arthritis (PsA)) were included. Th1 (interferon γ, interleukin 2) and Th2 (interleukin 4, interleukin 5 and interleukin 10) cytokine mRNA levels from arthritic knee ST were quantified by using an optimised polymerase chain reaction method with a computerised analysis system. Protein levels of proinflammatory cytokines (interleukin 1, tumour necrosis factor α and interleukin 6) in synovial fluid were quantified with a specific ELISA test. RESULTS Th1 cytokines were detected in all of RA ST samples in contrast with 58% (interferon γ) and 71% (interleukin 2) of SpA samples. Th2 cytokines were expressed in 90% of RA ST samples, but the findings in SpA were interleukin 10 in 90%, interleukin 4 in 60% and interleukin 5 in 40% of ST samples. However, when the mRNA levels of each cytokine were quantified and corrected for T cell mRNA levels, only interferon γ levels were significantly higher in RA than in SpA (pCONCLUSION This study has detected both Th1 and Th2 cytokine gene expression in ST from RA and SpA patients. Synovium interferon γ mRNA levels and SF interleukin 1β protein levels were significantly higher in RA than in SpA, so reflecting the known proinflammatory activity of interferon γ through macrophage activation. Thus, the Th1 (interferon γ)/Th2 (interleukin 4) ratio is significantly higher in RA than in SpA ST. These data confirm previous studies on ST Th1/Th2 balance in RA and extend previous work in comparing ST RA with subgroups of SpA distinct of ReA.