Anti-Inflammatory Effects of α-Melanocyte-Stimulating Hormone in Celiac Intestinal MucosaColombo G. · Buffa R. · Bardella M.T. · Garofalo L. · Carlin A. · Lipton J.M. · Catania A.
Departments of aInternal Medicine and bGastroenterology, Ospedale Maggiore di Milano IRCCS, Milan, cDivision of Pathology, Università di Milano Bicocca, Monza, Italy; dZengen Inc., WoodlandHills,Calif.,USA
Objectives: The peptide α-melanocyte-stimulating hormone (α-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 α-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 α-MSH and melanocortin receptors (MCRs), and gene expression of α-MSH precursor pro-opiomelanocortin and MCRs; (2) α-MSH and inflammatory cytokine production by duodenal specimens in vitro, and the influence of synthetic α-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 α-MSH and cytokine production in vitro and the effect of α-MSH on gliadin-stimulated cytokine production. Results: Elements of a localized anti-inflammatory influence based on α-MSH and its receptors were found: duodenal mucosa showed immunostaining for α-MSH and two of its receptor subtypes, MC1R and MC5R. α-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 α-MSH in vitro. Conclusions: Presence of α-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.
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