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 (Tc) responses to the cytokine interleukin-1 beta (IL-1 beta) 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.) injection of IL-1 beta (1 micrograms/rat). However, responses to centrally administered IL-1 beta (5ng intracerebroventricular (i.c.v.)) were similar in both groups at this time. After 8-9 weeks of supplementation, n-3 supplemented animals exhibited attenuated responses to both ip IL-1 beta (VO2 responses reduced by 68% and Tc by 0.8 degrees C) and also i.c.v. IL-1 beta (VO2 responses reduced by 56% and Tc by 0.7 degrees C). N-3 supplementation did not, however, influence the thermogenic capacity of these animals since responses to noradrenaline were similar in control and n-3 fed animals (50% increase in VO2). These findings demonstrate that n-3 supplementation modifies the pyrogenic and thermogenic responses to IL-1 beta, probably via changes in eicosanoid metabolism. Modification of central responses to IL-1 are delayed compared to the effects of peripheral administration indicating separate mechanisms of IL-1 on fever and thermogenesis in the brain and the periphery.