INHIBITION OF THE THERMOGENIC AND PYROGENIC RESPONSES TO INTERLEUKIN-1-BETA IN THE RAT BY DIETARY N-3 FATTY-ACID SUPPLEMENTATION

The thermogenic (increase in oxygen consumption, VO2) and pyrogenic (T c) responses to the cytokine interleukin-1beta (IL-1beta) were studied in rats fed a n-3 fatty acid supplemented diet (8.75% n-3 fatty acids /kg diet). 4-6 weeks after commencing the diets, the n-3 supplemented rats exhibited reduced pyrogenic (0.5 +/- 0.1-degrees-C versus 1.1 +/- 0.2-degrees-C in control animals) and thermogenic (9 +/- 3% versus 22 +/- 6% in control animals) responses to intraperitoneal (i.p.) inject ion of IL-1beta (1 mug/rat). However, responses to centrally administe red IL-1beta (5ng intracerebroventricular (i.c.v.)) were similar in bo th groups at this time. After 8-9 weeks of supplementation, n-3 supple mented animals exhibited attenuated responses to both ip IL-1beta (VO2 responses reduced by 68% and Tc by 0.8-degrees-C) and also i.c.v. IL- 1beta (VO2 responses reduced by 56% and Tc by 0.7-degrees-C). N-3 supp lementation did not, however, influence the thermogenic capacity of th ese animals since responses to noradrenaline were similar in control a nd n-3 fed animals (50% increase in VO2). These findings demonstrate t hat n-3 supplementation modifies the pyrogenic and thermogenic respons es to IL-1beta, probably via changes in eicosanoid metabolism. Modific ation of central responses to IL-1 are delayed compared to the effects of peripheral administration indicating separate mechanisms of IL-1 o n fever and thermogenesis in the brain and the periphery.