COCAINE INHIBITS HUMAN ENDOTHELIAL-CELL IL-8 PRODUCTION - THE ROLE OFTRANSFORMING GROWTH FACTOR-BETA

Cocaine use is associated with modulation of a broad range of biologic al functions including the capacity to influence cytokine production i n murine and human immunoeffector cells. Little is known, however, reg arding the effects of cocaine on endothelial cell cytokine production, Because the vascular endothelium actively participates in acute and c hronic inflammatory responses and interleukin-8 (IL-8) is one of the k ey cytokines involved in the inflammatory process, modification of the production of IL-8 by vascular endothelial cells may interfere with t he host response to infection or tissue injury. We investigated the ef fect of cocaine on endothelial cell IL-8 production. Conditioned super natant from EA.hy 926 cells were evaluated by ELISA following in vitro cocaine exposure. Cocaine decreased IL-8 production in a dose-respons ive manner, and this reduction correlated with down-regulation of IL-8 mRNA expression, Cocaine also increased the production of TGF-beta by EA.hy 926 cells and anti-TGF-beta abrogated the cocaine-mediated decr ement of IL-8 production, indicating that cocaine down-regulates endot helial IL-8 production by increasing TGF-beta. Our findings suggest th at the immuno-modulatory effects of cocaine may be mediated, in part, by modification of endothelial-derived cytokine production. (C) 1997 A cademic Press.