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.
Dr. Anna Catania
Medicina Interna I, Pad. Granelli
Ospedale Maggiore di Milano IRCCS, Via F. Sforza 35
I–20122 Milano (Italy)
Tel./Fax +39 02 5503 3318, E-Mail firstname.lastname@example.org
Received: March 6, 2002
Accepted: June 3, 2002
Number of Figures : 6, Number of Tables : 0, Number of References : 32
Official Journal of the International Society for Neuroimmunomodulation
Vol. 10, No. 4, Year 2002/2003 (Cover Date: Released February 2003)
Journal Editor: G.P. Chrousos, Bethesda, Md.
ISSN: 1021–7401 (print), 1423–0216 (Online)
For additional information: http://www.karger.ch/nim