Influence of unsaturated fatty acids on the production of tumour necrosis factor and interleukin-6 by rat peritoneal macrophages

摘要

The effect of individual unsaturated fatty acids on the release of tumour necrosis factor (TNF) and interleukin 6 (IL6) was in-vestigated in thioglycollate—induced rat peritoneal macrophages. The intracellular mechanisms associated with the changes of cytokine production in response to fatty acids were also studied. Incubation of macrophages with 100 uM docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) increased TNF (21 % and 15% respectively) and IL6 (69% and 40% respectively) production. Linoleic acid (LA) diminished TNF production by 16%. At 100 uM oleic acid (OA), LA and EPA concentration an increase in macrophage adenylate cyclase activity (110%, 72% and 39% respectively) and a decrease (14%) in the presence of DHA was observed. PGE2 production in the presence of 100 uM DHA was reduced by 36%, whereas in the presence of 100 uM LA an increase (75%) was observed. Phospholipase A2 (PLA2) activity was also found to be modified in the presence of EPA and DHA at 50 uM (20% and 60% respectively) and 100 uM (34% and 62% respectively) concentrations. The activities of both protein kinase A (PKA) and protein kinase C (PKC) were effected by the different fatty acids. At 50 uM all fatty acids suppressed PKA activity except OA which enhanced PKA activity by 14%. At 100 uM fatty acid concentration, EPAsuppressed PKA activity by 40%. PKC activity was enhanced by LA and OA, by 18 % and 21 % respectively. However, at 100 uM EPA and DHA, PKC activity was suppressed by 37% and 17% respectively, whereas PKC activity was enhanced by 146% in the pres-ence of 100 uM LA. These results show for the first time that unsaturated fatty acids have an effect on macrophage PLA2 activ-ity and that PGE2 may be a potent modulator of IL6 production. From these studies it is tempting to speculate that macrophage TNF and IL6 release may, in part, occur via a PKC and PKA independent pathway and that PLA2 activity and PGE2 concentra-tion are inversely related to production of TNF and IL6.