Anorexia in a rat model of colitis: interaction of interleukin-1 and hypothalamic serotonin

Abstract

Background and aims: Anorexia induced by experimental colitis in rats is mediated, in part, by increased release of serotonin (5-HT) from the hypothalamic paraventricular nucleus (PVN). In this model, anorexia is attenuated by treatment with an interleukin-1 (IL)-1 receptor antagonist (ra). However, a functional link between central IL-1 receptors and 5-HT release remains unproven. We have tested the hypothesis that anorexia associated with experimental colitis is mediated by IL-1 induced release of 5-HT.

Methods: In vivo 5-HT release in the PVN was measured in rats with 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis, treated with intracerebroventricular infusion of IL-1ra or vehicle treated controls. The effect of inhibition of tumour necrosis factor-alpha on food intake and PVN 5-HT release in TNBS-colitis was also tested.

Results: In rats with TNBS-induced colitis, intracerebroventricular infusion of IL-1ra resulted in a 18-fold reduction in PVN 5-HT release compared to vehicle-treated controls. This was associated with a significant increase in food intake in IL-1ra treated rats. In contrast intracerebroventricular administration of anti-tumour necrosis factor antibodies had no effect on either PVN 5-HT release or food intake in rats with TNBS-induced colitis.

Conclusions: In animals with TNBS-colitis, anorexia is mediated, in part, by the stimulatory effect of IL-1 on medial hypothalamic 5-HT.