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P037. Role of ghrelin and melatonin in pathogenesis of clinical and experimental inflammatory bowel disease

P. Konturek1, P. Celinski2, A. Madro2, T. Brzozowski3, S. Konturek3, 1Thuringia Clinic, Department of Internal Medicine, Saalfeld, Germany, 2Medical Academy Lublin, Department of Gastroenterology, Lublin, Poland, 3University Cracow, Institute of Physiology, Cracow, Poland

Background

Weight loss, malnutrition and disruption of circadian rhythms are frequently observed in patients with inflammatory bowel disease (IBD). Ghrelin and melatonin play important role in the regulation of food intake and are synthesized in gastrointestinal tract. However, the role of these hormones in pathogenesis of IBD has been little studied. The aims of this study were three-fold; (1) to assess the changes in the plasma level of melatonin in patients with active IBD; (2) to compare the changes in the expression of mRNA for ghrelin and TNF-α in the inflamed colonic mucosa of IBD patients with that of not inflammed control subjects; and (3) to analyze the expression of ghrelin- and TNF-α mRNA in the colonic mucosa of rats with experimentally induced TNBS-colitis.

Methods

The plasma samples were obtained from 10 patients with Crohn's disease, 17 patients with ulcerative colitis and 10 controls. The measurement of ghrelin and melatonin was performed by ELISA and RIA, respectively. In addition, the mucosal colonic samples obtained during colonoscopy from patients with ulcerative colitis and Crohn's disease were analyzed for the expression of TNF-α and ghrelin mRNA by RT-PCR. Finally, the colonic mucosal mRNA expression of TNF-α and ghrelin was assessed in TNBS-induced experimental colitis at days 3, 7, 10 and 14 after intrarectal TNBS administration.

Results

In comparision to controls, patients with IBD show decreased level of ghrelin (controls 332 pM/l vs CD 192.9 pM/l vs UC 179.4 pM/l) and increased level of melatonin (controls 12.2 pM/l vs CD 32.2 pM/l vs UC 26.11 pM/l). The expression of mRNA for TNF-α and ghrelin in colitis was significantly increased as compared to the intact mucosa of healthy controls. In rats with TNBS-colitis, the significant increase of TNF-α and ghrelin mRNAs expression was observed with a peak at day 7 to decrease toward the level in control mucosa at day 14.

Conclusion

Conclusions:

  1. The decrease in plasma levels of ghrelin in IBD patients could explain the loss of appetite, weight loss and malnutrition in IBD patients as compared to healthy controls.
  2. The overexpression of ghrelin in inflamed mucosa correlates with the abundant expression of TNF-α reflecting the possible role of ghrelin as proinflammatory marker and mediator of colonic inflammation.
  3. The release of melatonin is significantly increased in IBD patients and this could play an important role in the activation of the mucosal free radical scavenging system during colonic inflammation.