Anti-inflammatory effects of alpha-melanocyte-stimulating hormone in celiac intestinal mucosa.
OBJECTIVE
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.
Colombo
Gualtiero
G
Department of Internal Medicine, Ospedale Maggiore di Milano IRCCS, Milan, Italy.
Buffa
Roberto
R
Bardella
Maria Teresa
MT
Garofalo
Letizia
L
Carlin
Andrea
A
Lipton
James M
JM
Catania
Anna
A
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D002446:Celiac Disease / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004386:Duodenum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005903:Gliadin / Q000037:antagonists & inhibitors / Q000633:toxicity; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011979:Receptors, Pituitary Hormone / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism* / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D005903:Gliadin; D015850:Interleukin-6; D011333:Pro-Opiomelanocortin; D011979:Receptors, Pituitary Hormone; D000521:alpha-MSH; D000093242:Interleukin-6 Inhibitors; C029446:MSH receptor