An Interleukin 1 Inhibitor Affects both Cell-Associated Interleukin 1-Induced T Cell Proliferation and PGE 2/Collagenase Production by Human Dermal Fibroblasts and Synovial Cells

Abstract

Lipopolysaccharide (LPS) induces cell-associated interleukin 1 (IL 1) production in the human promonocytic cell line U937. Demonstration of cell-associated IL 1 activity was based on the ability of LPS-treated U937 cells, subsequently fixed with paraformaldehyde, to stimulate thymocyte proliferation in the presence of phytohemagglutinin. Like soluble IL 1 (sIL 1), cell-associated IL 1 is capable of inducing PGE 2 and/or collagenase production by dermal fibroblasts and human synovial cells in a dose-dependent manner. It is thus a mediator of the inflammatory response owing to a direct intercellular contact located at the membrane level, where bound molecules may trigger inflammation at a local site of action. We reported that the natural (~ 23 kDa) IL 1 inhibitor (IL I INH) from the urine of febrile patients inhibited all the sIL-1-induced biologic activities under investigation and that it acted by binding to the IL 1 receptor, thus blocking the interaction of the monokine with the receptor. Data demonstrate that the IL 1 INH also blocks cell-associated IL 1-induced T cell proliferation and PGE 2 production by both dermal fibroblasts and synovial cells as well as collagenase production by the latter cell type. Thus, as for the sIL 1, a feedback mechanism exists for cellassociated IL 1-induced bioactivities.