In vivo anti-inflammatory effects of the M20 IL-1 inhibitor: II. Effects on serum reactants

Abstract

We have previously described an IL-1 Inhibitor derived from the M20 myelomoncytic cell line. This line also secretes several molecules of IL-1. We have shown that this factor is specific to IL-1 in vitro, as well as in vivo. In vitro IL-1 induced proliferative responses of mouse thymocytes, human T cells and fibroblasts and IL-1 stimulated PGE2 secretion from fibroblasts, were all inhibited by the M20 IL-1 Inhibitor. In vivo, the IL-1 Inhibitor reduced parameters of acute inflammation such as fever, leukocytosis and local inflammation. This study describes additional effects of the M20 IL-1 Inhibitor on inflammatory serum reactants. Levels of corticosterone and fibrinogen were increased by injection of IL-1, and decreased by the IL-1 Inhibitor. IL-1 reduced zinc and iron plasma levels and elevated copper plasma levels. The M20 IL-1 Inhibitor reversed these changes in a dose dependent manner. Similar effects produced by IL-6 and TNF were unaffected by the M20 IL-1 Inhibitor. Our results indicate that the M20 IL-1 Inhibitor acts specifically on IL-1 induced responses in vivo. Therefore we conclude that this IL-1 Inhibitor has a great potential as an anti-inflammatory agent.