INDUCTION OF IL-4 BY PLATELET-ACTIVATING-FACTOR

Platelet-activating factor (PAF) is a phospholipid inflammatory mediat or which is synthesized by a variety of cells, including monocytes, en dothelial cells, mast cells and neutrophils. PAF acts via a recently c loned PAF receptor, present on monocytes and endothelial cells, but no t on nonactivated lymphocytes. IL-4 is mainly produced by T lymphocyte s, and belongs to the Th2 subset of T helper cells. IL-6 is mainly a m onocyte/macrophage-derived cytokine with multiple proinflammatory effe cts. We here report that PAF induces IL-4 production, as determined by ELISPOT. Antibodies to MHC class II inhibited the IL-4 stimulatory ef fects of PAF. PAF also had the capacity to induce IgA production, as d etermined by ELISPOT, and IL-6 production in peripheral blood mononucl ear cells (PBMC) as determined by ELISA. These PAF-mediated effects we re completely inhibited by a specific PAF-receptor antagonist, WEB 217 0. Taken together, our data indicate that PAF activates T lymphocytes to IL-4 production by an indirect, monocyte-dependent mechanism depend ent on MHC class II. PAF also enhances antibody formation and IL-6 pro duction from PBMC. These findings indicate that PAF activates immune-c ompetent cells, which may be of importance in inflammatory diseases su ch as asthma, vasculitis and atherosclerosis.