MODE OF FOOD-INTAKE REDUCTION IN LEWIS RATS WITH INDOMETHACIN-INDUCEDULCERATIVE ILEITIS

The mechanism of anorexia in inflammatory bowel disease is poorly unde rstood. To gain insight into possible pathophysiologic mechanisms, the feeding indices and food intake were studied in an animal model of Cr ohn's disease. The anorexia of indomethacin-induced ulcerative ileitis was compared with that of the well-known anorexia of total parenteral nutrition (TPN). Forty-five female Lewis rats were randomized to four groups: Control, Indomethacin, Indomethacin + TPN, and TPN. Feeding i ndices and food intake were continuously measured using the Automated Computerized Rat Eater Meter. Interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E(2) (PGE(2)), and le ukotriene B-4 (LTB(4)) were assayed in plasma, mononuclear cell cultur e, or ileum to determine their role in mediating anorexia. In the TPN group, spontaneous food intake (SFI) decreased (52%; p < 0.05), primar ily via reduction in meal number (MN, 54%; p < 0.05) and, to a lesser extent, meal size (MZ, 35%; p < 0.05). In comparison, in the Indometha cin group SFI decreased (74%; p < 0.05) primarily via reduction in MZ (67%, p < 0.05); MN also decreased but to a lesser extent (27%; p < 0. 05). In the Indomethacin + TPN group, SFI decreased (55%; p > 0.05) pr imarily via reduction in MN (79%; p < 0.05), whereas MZ decreased slig htly (19%; p < 0.05). Only in the Indomethacin group were IL-1 alpha a nd TNF-alpha detected in the mononuclear cell culture and plasma, resp ectively. In the Indomethacin group, an inverse correlation existed be tween MZ and TNF-alpha (p < 0.05). In the Indomethacin group, IL-1 alp ha, PGE(2), and LTB(4) concentrations did not correlate with feeding i ndices. SFI reduction in this model was mediated primarily via a decre ase in MZ. TNF-alpha is proposed to mediate this effect and TPN was sh own to overcome the effect on MZ.