title: Interleukin-1-induced anorexia in the rat. Influence of prostaglandins.
abstract: The anorexia associated with acute and chronic inflammatory or infectious conditions is poorly understood. Our objectives were to explore the anorexigenic effects of interleukin-1 (IL-1) in the rat. Recombinant human (rh) IL-1 beta, murine (rm) IL-1 alpha and to a lesser extent rhIL-1 alpha significantly reduced food intake at greater than or equal to 4.0 micrograms/kg i.p. but not at lower doses, in young (200-250 g) meal-fed rats on chow diets. The anorexic effect appears to be mediated by prostaglandins since pretreatment with ibuprofen completely blocked it, and a fish oil based diet abolished it, in comparison to corn oil or chow diets. Fish oil feeding also decreased basal and IL-1 stimulated prostaglandin E2 production by tissues in vitro (liver, brain, peritoneal macrophages) and in the whole body. Constant intravenous infusions of lower doses of IL-1 also diminished food intake, though intravenous boluses did not (reflecting rapid renal clearance). Chronic daily administration of IL-1 caused persistent inhibition of food intake for 7-17 d in chow and corn oil fed rats, but had no effect in fish oil fed rats. There was an attenuation of the effect (tachyphylaxis) after 7 d in corn oil and chow fed rats, but slowed weight gain and lower final weights were observed after 17-32 d of daily IL-1. Old (18-20 mo Fisher 344) rats showed less sensitivity to IL-1 induced anorexia. In conclusion, IL-1 is anorexigenic in the rat, but this is influenced by the structural form of IL-1, the route and chronicity of administration, the source of dietary fat, and the age of the animal. The ability of prior fat intake to influence the anorexic response to IL-1 represents a novel nutrient-nutrient interaction with potential therapeutic implications.
authors: U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts.
authors: M K
authors: MK
authors: Hellerstein
authors: S N
authors: SN
authors: Meydani
authors: M
authors: M
authors: Meydani
authors: K
authors: K
authors: Wu
authors: C A
authors: CA
authors: Dinarello
mesh_terms: D000818:Animals; D000855:Anorexia / Q000209:etiology*; D001933:Brain Stem / Q000378:metabolism; D004435:Eating; D001068:Feeding and Eating Disorders / Q000209:etiology*; D007052:Ibuprofen / Q000494:pharmacology; D007249:Inflammation / Q000150:complications; D007375:Interleukin-1 / Q000494:pharmacology*; D007962:Leukocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis* / Q000378:metabolism / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains
chemical_list: D007375:Interleukin-1; D011453:Prostaglandins; D007052:Ibuprofen