Lysophosphatidylcholine induces the production of IL-1β by human monocytes Original Research Article

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 cytokine production by human monocytes. Among all the cytokines tested (IL-8, TNFα, MCP-1 and IL-1β), we found that lysoPC most consistently stimulated human monocytes to produce IL-1β in a dose and time dependent manner. Adherent monocytes were exposed to lysoPC in cell culture medium containing 0.5% bovine serum albumin. When exposed to lysoPC from 12.5 to 75 μM, the cellular content of IL-1β increased 2–4 fold. Up to a concentration of 50 μM no cytotoxic effect could be seen. Over 50 μM there was evidence of toxicity. The level of IL-1β reached its highest level at 24 h and then declined. At 48 h, the cell associated IL-1β was low, but still the lysoPC stimulated cells produced 4.1 times more IL-1β than controls. Also the IL-1β mRNA was augmented by lysoPC in parallel with the IL-1β protein levels. The stimulatory effect of lysoPC was dependent on its chain length. There was no effect on IL-1β production when the acyl chain was shorter than 16. We also found that saturated lysoPC 18:0 stimulated IL-1β production more than the monounsaturated lysoPC 18:1. Thus, the lysoPC in oxidatively modified LDL may stimulate the production of IL-1β in macrophages, which may contribute to the inflammatory response in atherosclerotic tissue.