Abstract
BACKGROUND: Although leptin, an adipocyte derived hormone which regulates food intake and energy balance, is released after injections of tumour necrosis factor (TNF) and interleukin 1, plasma concentrations have not been characterised in chronic inflammation. Leptin may contribute to the anorexia and body weight loss associated particularly with the acute stages of inflammatory bowel disease. AIMS: To investigate plasma leptin concentrations during the time course of intestinal inflammation in different animal models. METHODS: Plasma leptin was measured at different time points in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis, indomethacin induced ileitis, or endotoxic shock caused by lipopolysaccharide (LPS). Systemic TNF-alpha was also measured during acute inflammation. RESULTS: Plasma leptin concentrations increased fourfold eight hours after induction of TNBS colitis (p<0.0001) and twofold after administration of ethanol alone (p<0.02). Plasma leptin responses throughout the first post-treatment day were correlated with myeloperoxidase activity and gross damage scores. Similar leptin overexpression was observed in indomethacin induced ileitis and in rats with endotoxic shock. Plasma concentrations were lower in TNBS treated rats than in controls on day 5 before reaching a similar concentration on day 14. Anorexia and body weight loss were observed during the first four days post-TNBS. A significant increase in systemic TNF-alpha was only detected in LPS treated rats. CONCLUSION: Elevated plasma leptin concentrations, correlated with the degree of inflammation and associated with anorexia, were induced in rats during the early stages of experimental intestinal inflammation but proved transient; this might account for discrepancies in recent results concerning concentrations in patients with inflammatory bowel diseases.