Fatty Acid Modulation of Cytokine Release from Human Monocytic Cells

The effect of individual fatty acids on the release of interleukin-1-like (IL-1-like) cytokine activity was investigated on human monocytic cells, primarily the cell line U937 and also peripheral blood monocytes. IL-1-like bioactivity was estimated by assessing the effect of supernatants from monocytic cells on the proliferation of thymocytes as measured by [3H]thymidine incorporation into the acid insoluble fraction of the thymocytes. A pronounced concentration-dependent increase (in the range 1-100 microM) in the release of IL-1-like activity was observed with arachidonic acid, dihomo-gamma-linolenic acid (DGLA) and eicosapentaenoic acid (EPA) in absence and presence of bacterial endotoxin (LPS). A much less pronounced concentration-dependent increase in the release of IL-1-like activity was observed with oleic acid and linoleic acid had only a small effect at 100 microM. The potencies of each fatty for this effect using the EC50 concentrations were arachidonic acid > EPA > or = DGLA > linoleic acid > oleic acid with palmitic acid having no effect. The IL-1-like activity was confirmed by the attenuation of the monocytic-cell-supernatant-induced increase in thymocyte proliferation by anti-IL-1 beta antiserum. An increase in the release of anti-IL-1 beta-antiserum-precipitable radioactivity from U937 cells prelabelled with [35S]methionine then incubated with fatty acids in the presence of LPS further confirmed that IL-1 release was increased. Arachidonic acid and EPA also increased the release of IL-1-like activity from peripheral blood monocytes demonstrating that normal monocytes can respond in a similar manner and that this effect of the fatty acids is not restricted to the U937 cell line.