EXPRESSION OF INTERFERON-GAMMA (IFN-GAMMA), IL-10, IL-12 AND TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) MESSENGER-RNA IN SYNOVIAL-FLUID CELLS FROM PATIENTS IN THE EARLY AND LATE PHASES OF RHEUMATOID-ARTHRITIS (RA)

The expression of immunoregulatory cytokines was investigated in fresh ly isolated synovial fluid mononuclear cells (SFMC) and peripheral blo od mononuclear cells (PBMC) from patients with RA, using a quantitativ e reverse transcriptase-polymerase chain reaction (RT-PCR) assay. IFN- gamma, TGF-beta, IL-10 and IL-12 (p40) transcripts were detected in SF MC of patients with early disease (<1 year duration) as well as in pat ients with long standing arthritis (>1 year). The expression of IFN-ga mma, IL-10 and IL-12 mRNA was increased in SFMC compared with RA PBMC. In addition, the expression was higher in RA SFMC than in PBMC from h ealthy control individuals. Immunoassay analysis of the secreted IL-12 heterodimer demonstrated increased levels in RA SF compared with leve ls found in serum from RA patients and control individuals. High level s of TGF-beta mRNA were found in SFMC, but a significantly decreased T GF-beta/beta(2)-microglobulin (beta(2)-M) ratio was found compared wit h PBMC from both patients and control individuals. IL-4 mRNA could not be detected, either in SFMC or in PBMC. Cytokine expression in RA PBM C did not differ from control PBMC, with the exception of a decreased TGF-beta/beta(2)-M ratio in RA patients with early disease. Our findin gs of IFN-gamma mRNA and IL-12, but undetectable levels of IL-4 mRNA, suggest that the synovitis is characterized by a type 1 immune respons e. The presence of TGF-beta and IL-10 mRNA indicates that immunosuppre ssive cytokines may also operate in the inflamed joint, although their level of expression may not be sufficient for down-modulation of immu ne activation.