Objectives: The peptide alpha-melanocyte-stimulating hormone (alpha-MSH) possesses potent anti-inflammatory activities and has been previously implicated in the endogenous control of inflammatory reactions. The aim of the present research was to determine whether alpha-MSH and its receptors participate in a localized anti-inflammatory response in the duodenal mucosa of celiac patients.
Methods: Three series of experiments were performed, using duodenal biopsy pairs from 53 adult celiac patients and 14 normal subjects, in order to determine: (1). mucosal immunoreactivity for alpha-MSH and melanocortin receptors (MCRs), and gene expression of alpha-MSH precursor pro-opiomelanocortin and MCRs; (2). alpha-MSH and inflammatory cytokine production by duodenal specimens in vitro, and the influence of synthetic alpha-MSH on such cytokine production, and (3). the influence of stimulation with gliadin (the subfraction of gluten that is toxic to patients with celiac disease) on alpha-MSH and cytokine production in vitro and the effect of alpha-MSH on gliadin-stimulated cytokine production.
Results: Elements of a localized anti-inflammatory influence based on alpha-MSH and its receptors were found: duodenal mucosa showed immunostaining for alpha-MSH and two of its receptor subtypes, MC1R and MC5R. alpha-MSH and MC1R immunoreactivity was more intense in specimens from celiac patients. Release of interleukin 6 from gliadin-stimulated duodenal mucosa was inhibited by synthetic alpha-MSH in vitro.
Conclusions: Presence of alpha-MSH and its receptors in celiac mucosa suggests the presence of a local reaction to control the inflammatory response elicited by gliadin. In selected cases of refractory celiac disease, treatment with exogenous peptides might be considered.
Copyright 2003 S. Karger AG, Basel