Intestinal inflammation influences I+/--MSH reactive autoantibodies: Relevance to food intake and body weight

Autoantibodies reacting with alpha-melanocyte-stimulating hormone ( alpha -MSH), an anorexigenic neuropeptide, are involved in regulation of feeding. In this work we studied if intestinal inflammation (mucositis) may influence alpha -MSH autoantibodies production relevant to food intake and body weight. Mucositis and anorexia were produced in Sprague-Dawley rats by methotrexate (MTX, 2.5 mg/kg/day, for three days, subcutaneously). Plasma levels of total IgG and of alpha -MSH autoantibodies were measured during and after MTX-induced mucositis and were compared with pair-fed and ad libitum-fed controls. Effects of intraperitoneal injections of rabbit anti- alpha -MSH IgG (3 or 10 mu g/day/rat) on MTX-induced anorexia and on plasma alpha -MSH peptide concentration were separately studied. Here we show that in MTX rats, intestinal mucositis and anorexia were accompanied by decreased plasma levels of both total IgG and of alpha -MSH autoantibodies while refeeding was characterized by their elevated levels. In spite of similar food intake in MTX and pair-fed rats, recovery of body weight was delayed by at least 1 week in the MTX group. During refeeding and body weight deficit in MTX rats, alpha -MSH IgG autoantibody levels correlated negatively with food to water intake ratios. Injections of anti- alpha -MSH IgG induced a dose-dependent attenuation of food intake and body weight regain in MTX-treated rats accompanied by increased concentrations of alpha -MSH peptide which correlated positively with plasma levels of alpha -MSH autoantibodies. These data show that intestinal inflammation, independently from food restriction, affects general humoral immune response which may influence food intake and body weight control via modulation of alpha -MSH plasma concentration by alpha -MSH reactive autoantibodies.