Leptin, which is a newly recognised ‘anorexic’ hormone produced mainly by adipose tissue, regulates food intake and energy balance. Plasma leptin concentrations increase acutely during infection and inflammation (Faggioni et al. 2001), suggesting a modulatory role of leptin in the hypothalamo-pituitary-adrenal (HPA) stress axis as an acute phase reactant (Maruna et al. 2001). It is well known that HPA axis and glucocorticoids have a proliferative activity on the immune system, while stress-induced overactivity of the HPA axis suppresses the immune response. However, it is not clear yet whether leptin has a pro-inflammatory (Barbier et al. 2001) or an anti-inflammatory (Brzozowski et al. 2001) activity in the pathogenesis of intestinal inflammation. Therefore, the present study was designed to investigate the effect of leptin on acute colonic inflammation and this effect was compared with that of acute stress, which is known to act via the HPA axis.

Experimental procedures were approved by the Marmara University Animal Care and Use Committee. After an overnight fast, Sprague-Dawley rats of both sexes (200Ð250 g; n = 59) were administered intrarectally (I.R.) under light ether anaesthesia with 4 % (1 ml) acetic acid (colitis) (Sekizuka et al. 1988) or saline (control). Some rats were subjected to water avoidance stress for 30 min at the sixth hour following the administration of acetic acid or saline. Leptin (10 mg kg^-1; I.P.) or saline was injected immediately before and 6 h after the I.R. administrations. Rats were humanely decapitated at 24 h and the distal 8 cm of the colon were removed for macroscopic scoring and the determination of tissue wet weight index (WWI) and tissue myeloperoxidase activity (MPO; an indicator of tissue neutrophil infiltration). Data are means ± S.E.M. from 7Ð9 rats in each group and were analysed using ANOVA.

Acetic acid-induced colitis increased the macroscopic damage score (4.8 ± 0.6, P < 0.001), compared with control group (0.06 ± 0.06), as well as WWI (P < 0.001) and MPO activity (P < 0.05). Water avoidance stress in the control group had no significant effect, while its application in the colitis group reduced both macroscopic score (2.4 ± 0.3, P < 0.01) and WWI (P < 0.01). Similarly, in the leptin-treated colitis group, macroscopic score (2.8 ± 0.4, P < 0.05) and WWI (P < 0.01) were also reduced, but leptin per se had no effect on control animals (0.06 ± 0.04). When leptin treatment and stress were applied together in the colitis group, the reductions in the macroscopic score and WWI accomplished by either leptin or stress, were abolished. However, increased MPO activity in the colitis group was not affected by stress or leptin.

Our results indicate that leptin has an anti-inflammatory effect on acetic acid-induced colitis and this effect appears to be independent of neutrophils. Based on our present results, it may be speculated that leptin, acting via the HPA axis, has an immunomodulatory and an anti-inflammatory effect. However, when the HPA axis is over-stimulated by leptin during stressful conditions, immune dysfunction is likely. This supports the fact that the anorexia during acute infection, which is beneficial in the beginning, turns out to be deleterious in chronic infections and neoplastic diseases.

All procedures accord with current local guidelines.