INTERLEUKIN-6 INDUCES THE SYNTHESIS OF TISSUE INHIBITOR OF METALLOPROTEINASES-1/ERYTHROID POTENTIATING ACTIVITY (TIMP-1/EPA)

The study examines the role of interleukin-6 (IL-6) in connective tissue metabolism. Effects of different preparations of IL-6 on production of collagenase and tissue inhibitor of metalloproteinases-1/erythroid potentiating activity production are studied in human fibroblasts, synoviocytes, and articular chondrocytes. In contrast to interleukin-1-beta (IL-1-beta) and tumor necrosis factor-alpha (TNF-alpha), IL-6 does not stimulate the production of collagenase, nor does it modulate the stimulatory effects of IL-1-beta and TNF-alpha on the production of this proteinase. Furthermore, IL-6 has no detectable effect on prostaglandin E2 production, and additional proinflammatory response induced by IL-1-beta and TNF-alpha. IL-6, however, is identified as a potent inducer of de novo synthesis of tissue inhibitor of metalloproteinases-1/erythroid potentiating activity in all types of connective tissue cells examined. These results define new biological activities of IL-6 and provide further insight into the regulation of connective tissues by cytokines.