Use of ghrelin as a treatment for inflammatory bowel disease: mechanistic considerations

Abstract

Inflammatory bowel diseases (IBD)-and in particular Crohn's disease-are immune-mediated processes that result in denuded intestinal mucosa and can produce decreased appetite, weight loss, and systemic inflammation. Current treatments include anti-inflammatory medications, immunomodulators, and feeding interventions. Ghrelin is an endogenous orexigenic hormone that directly stimulates growth hormone release, increases gut motility, and has cardiovascular and anti-inflammatory properties. Although ghrelin levels are elevated in active IBD, administration of ghrelin in most (but not all) animal models of colitis has produced improvements in disease activity and systemic inflammation. The mechanism for these effects is not known but may relate to decreased inflammation, increased motility, increased appetite, and increased colonic blood flow. Human trials have not been performed, however, and more research is clearly needed.

Figure 1

Efficacy of ghrelin as a treatment for TNBS colitis. For each set of experiments shown, TNBS colitis was induced via intrarectal injection on day 0 while control mice received 50% ethanol. Mice in (a) were given ghrelin as a rescue medication on days 6–9 of colitis and exhibited a rapid improvement in weight and in macroscopic score. Mice in (b) and (c) were given a single ghrelin injection 12 hours after TNBS treatment and had histology (b) and serum cytokines (c) examined on day 3 after treatment. *P < 0.05 versus TNBS (adapted from Gastroenterology 130: 1707–1720, used by permission).

Figure 2

Potential mechanisms of ghrelin action in colitis. Ghrelin acts on the GHSR-1a in widespread tissues, causing several effects that might contribute to efficacy in features of IBD (adapted from Nature Clinical Practice 2: 459–466, used by permission).