Mode of food intake reduction in Lewis rats with indomethacin-induced ulcerative ileitis

Abstract

The mechanism of anorexia in inflammatory bowel disease is poorly understood. To gain insight into possible pathophysiologic mechanisms, the feeding indices and food intake were studied in an animal model of Crohn'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 indices and food intake were continuously measured using the Automated Computerized Rat Eater Meter. Interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), prostaglandin E 2 (PGE 2), and leukotriene B 4 (LTB 4) were assayed in plasma, mononuclear cell culture, or ileum to determine their role in mediating anorexia. In the TPN group, spontaneous food intake (SFI) decreased (52%; p < 0.05), primarily 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 Indomethacin 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) primarily via reduction in MN (79%; p < 0.05), whereas MZ decreased slightly (19%; p < 0.05). Only in the Indomethacin group were IL-1α and TNF-α detected in the mononuclear cell culture and plasma, respectively. In the Indomethacin group, an inverse correlation existed between MZ and TNF-α ( p < 0.05). In the Indomethacin group, IL-1α, PGE 2, and LTB 4 concentrations did not correlate with feeding indices. SFI reduction in this model was mediated primarily via a decrease in MZ. TNF-α is proposed to mediate this effect and TPN was shown to overcome the effect on MZ.