Anorexia in a rat model of colitis: interaction of interleukin-1 and hypothalamic serotonin.
OBJECTIVE
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.
El-Haj
Tarek
T
Department of Adult and Paediatric Gastroenterology, St. Bartholomew's and The Royal London School of Medicine and Dentistry, 2 Newark Street, London E1 2AT, UK.
Poole
Stephen
S
Farthing
Michael J G
MJ
Ballinger
Anne B
AB
D000818:Animals; D000855:Anorexia / Q000276:immunology* / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000276:immunology; D007276:Injections, Intraventricular; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D015213:Neuroimmunomodulation / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000906:Antibodies; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; D014302:Trinitrobenzenesulfonic Acid