REDUCTION IN FOOD AND WATER-INTAKE INDUCED BY MICROINJECTION OF INTERLEUKIN-1-BETA IN THE VENTROMEDIAL HYPOTHALAMUS OF THE RAT

Interleukin-1 (IL-1) is a cytokine which is released during immune activation and mediates some of the host's responses to infection and inflammation. Increasing evidence suggests that it also has a role as an intrinsic neuromodulator in the central nervous system. We report here that microinjections of 5 and 30 ng (286 fmol and 1.71 pmol) of recombinant human IL-1 beta in the ventromedial nucleus of the hypothalamus (VMH) of adult male rats time- and dose-dependently induce anorexia and weight loss in two experimental paradigms: rats allowed free-access to food and water and food-restricted rats trained to press a lever for food on a fixed ratio 10 schedule. IL-1 beta (5 ng) diminished food and water consumption by 45 and 30%, respectively, and decreased body weight for at least 24 h postinjection in rats fed ad lib. These effects were more severe and lasted at least 48 h after infusion of the larger dose of 30 ng. The IL-1 beta-induced anorexia and weight loss were neither as large nor as long-lasting in food-restricted rats. Operant responding for food was decreased 2-4 h postinfusion of 5 ng IL-1 beta and 2-8 h after 30 ng IL-1 beta, but in both cases returned to baseline within 24 h. Body weight was decreased compared to saline injections from 4 to 24 h postinfusion. Nevertheless, when allowed to eat ad lib for the 24 h immediately following the behavioral testing, body weight returned to control (5 ng) or near control levels (30 ng). These results support the hypothesis that the VMH may serve as a central site of action for the depressive effects of IL-1 beta on food and water intake and body weight.