GROWTH-FACTOR ACTIVITY OF IL-6 IN THE SYNOVIAL-FLUID OF PATIENTS WITHRHEUMATOID-ARTHRITIS

Objective. We set out to determine whether the ability of synovial flu ids (SF) in patients with rheumatoid arthritis (RA) to facilitate the proliferation of synovial tissue-derived fibroblastic cell lines was r elated to the presence of growth factors and/or cytokines. Methods. Th e growth factor activity of 20 RA SF was measured by their ability to induce anchorage-independent growth of the rat NRK-49F (49F) fibroblas tic strain. The presence of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) was also assessed using neu tralising anti-TGF-beta or anti-PDGF-AB mAbs. Cytokines were measured by functional assays or ELISA. Results. We observed a correlation betw een growth factor activity and the IL-6 levels in SF. Both were correl ated to the erythrocyte sedimentation rate (ESR) and C-reactive protei n (CRP) levels in SF and serum. IL-6(at concentrations above 10(4) U/m l), synergized with growth factors in the induction of the anchorage i ndependent (AI) growth of 49F cells. Pre-treatment of SF with a neutra lising anti-IL-6 mAb substantially reduced the capacity of these SF to induce AI growth of 49F cells, confirming the growth factor activity of IL-6 in this test. In contrast, IL-6 alone or in association with P DGF, epidermal growth factor (EGF) or TGF-P had no effect on the ancho red growth of synovial tissue-derived fibroblasts, and treatment of SF with a neutralising anti-IL-6 mAb did not affect their ability to inc rease the growth rate of synovial tissue-derived fibroblasts. Conclusi ons. These results strongly suggest that IL-6 is responsible for the o bserved correlation between the growth factor activity of SF and infla mmatory indexes such as ESR and CRP. However, neither IL-6 nor PDGF we re responsible for the observed positive effect of SF on synovial fibr oblastic cell lines.