LYSOPHOSPHATIDYLCHOLINE INDUCES THE PRODUCTION OF IL-1-BETA BY HUMAN MONOCYTES

There is evidence for the presence of lysophosphatidylcholine (lysoPC) in oxidatively modified low density lipoprotein, human plasma and in atherosclerotic lesions. We studied the effect of lysoPC on the cytoki ne production by human monocytes. Among all the cytokines tested (IL-8 , TNF alpha, MCP-I and IL-1 beta), we found that lysoPC most consisten tly stimulated human monocytes to produce IL-1 beta in a dose and time dependent manner. Adherent monocytes were exposed to lysoPC in cell c ulture medium containing 0.5% bovine serum albumin. When exposed to ly soPC from 12.5 to 75 mu M, the cellular content of IL-1 beta increased 2-4 fold. Up to a concentration of 50 mu M no cytotoxic effect could be seen. Over 50 mu M there was evidence of toxicity. The level of IL- 1 beta reached its highest level at 24 h and then declined. At 48 h, t he cell associated IL-1 beta was low, but still the lysoPC stimulated cells produced 4.1 times more IL-1 beta than controls. Also the IL-1 b eta mRNA was augmented by lysoPC in parallel with the IL-1 beta protei n levels. The stimulatory effect of lysoPC was dependent on its chain length. There was no effect on IL-1 beta production when the acyl chai n was shorter than 16. We also found that saturated lysoPC 18:0 stimul ated IL-1 beta production more than the monounsaturated lysoPC 18:1. T hus, the lysoPC in oxidatively modified LDL may stimulate the producti on of IL-1 beta in macrophages, which may contribute to the inflammato ry response in atherosclerotic tissue. (C) 1998 Elsevier Science Irela nd Ltd. All rights reserved.