Effects of interleukin‐6 on the metabolism of connective tissue components in rheumatoid synovial fibroblasts

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Abstract
Objective. High levels of interleukin‐6 (IL‐6) have been found in the synovial fluid of patients with rheumatoid arthritis (RA). We undertook the present study to investigate the role of IL‐6 in this disease.Methods. We examined the effects of IL‐6, in comparison with IL‐1, on the biosynthesis of extracellular matrix macromolecules and of matrix‐degrading proteinases in rheumatoid synovial fibroblasts.Results. In rheumatoid synovial fibroblasts, IL‐6 by itself enhanced the production of plasminogen activator, its inhibitor, and tissue inhibitor of metalloproteinases, whereas it did not modulate the biosynthesis of precursor of matrix metalloproteinase 1 (proMMP‐1) (tissue collagenase), proMMP‐3 (stromelysin), or connective tissue components. However, IL‐1–induced production of proMMP‐1 and proMMP‐3 was preferentially augmented by IL‐6.Conclusion. These results suggest that in RA, IL‐6 may participate along with IL‐1 in fine tuning of the catabolism of connective tissue components, by modulating the balance between connective tissue–degrading enzymes and their inhibitors.

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