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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.

Type

Journal

Arthritis Rheum

Publication Date

10/1992

Volume

35

Pages

1197 - 1201

Keywords

Arthritis, Rheumatoid, Collagen, Connective Tissue, Extracellular Matrix, Fibroblasts, Glycoproteins, Glycosaminoglycans, Humans, Interleukin-1, Interleukin-6, Metalloendopeptidases, Plasminogen Activator Inhibitor 1, Synovial Membrane, Tissue Inhibitor of Metalloproteinases, Urokinase-Type Plasminogen Activator