Journal Mobile Options
Table of Contents
Vol. 10, No. 4, 2002/2003
Issue release date: February 2003
Neuroimmunomodulation 2002–03;10:208–216

Anti-Inflammatory Effects of α-Melanocyte-Stimulating Hormone in Celiac Intestinal Mucosa

Colombo 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

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


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.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Schuppan D: Current concepts of celiac disease pathogenesis. Gastroenterology 2000;119:234–242.
  2. Paulley LW: Observations on the aetiology of idiopathic steatorrhoea. BMJ 1954;2:1318–1321.
  3. Yardley JH, Bayless TM, Norton JH, Hendrix TR: Celiac disease: A study of the jejunal epithelium before and after a gluten-free diet. New Engl J Med 1962;267:1173–1179.
  4. Ferguson A, Murray D: Quantitation of intraepithelial lymphocytes in human jejunum. Gut 1971;12:988–994.
  5. Ferguson A, MacDonald TT, McClure JP, Holden RJ: Cell-mediated immunity to gliadin within the small-intestinal mucosa in coeliac disease. Lancet 1975;i:895–897.
  6. Nilsen EM, Jahnsen FL, Lundin KE, Johansen FE, Fausa O, Sollid LM, Jahnsen J, Scott H, Brandtzaeg P: Gluten induces an intestinal cytokine response strongly dominated by interferon-γ in patients with celiac disease. Gastroenterology 1998;115:551–563.
  7. Przemioslo RT, Kontakou M, Nobili V, Ciclitira PJ: Raised pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α in coeliac disease mucosa detected by immunohistochemistry. Gut 1994;35:1398–1403.
  8. Beckett CG, Dell’Olio D, Shidrawi RG, Rosen-Bronson S, Ciclitira PJ: Gluten-induced nitric oxide and pro-inflammatory cytokine release by cultured coeliac small intestinal biopsies. Eur J Gastroenterol Hepatol 1999;11:529–535.
  9. Catania A, Lipton JM: α-Melanocyte stimulating hormone in the modulation of host reactions. Endocr Rev 1993;14:564–576.
  10. Catania A, Airaghi L, Colombo G, Lipton JM: α-MSH in normal human physiology and disease states. Trends Endocrinol Metab 2000;11:304–308.
  11. Eberle AN: The Melanotropins. Basel, Karger, 1988.
  12. Lipton JM, Ceriani G, Macaluso A, McCoy D, Carnes K, Biltz J, Catania A: Antiinflammatory effects of the neuropeptide α-MSH in acute, chronic, and systemic inflammation. Ann NY Acad Sci 1994;741:137–148.
  13. Lipton JM, Catania A: Anti-inflammatory actions of the neuroimmunomodulator α-MSH. Immunol Today 1997;18:140–145.

    External Resources

  14. Macaluso A, McCoy D, Ceriani G, Watanabe T, Biltz J, Catania A, Lipton JM: Antiinflammatory influences of α-MSH molecules: Central neurogenic and peripheral actions. J Neurosci 1994;14:2377–2382.
  15. Catania A, Gerloni V, Procaccia S, Airaghi L, Manfredi MG, Lomater C, Grossi L, Lipton JM: The neuropeptide α-MSH in synovial fluid of patients with rheumatic diseases: Comparisons with other anticytokine molecules. Neuroimmunomodulation 1994;1:321–328.
  16. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–159.
  17. Star RA, Rajora N, Huang J, Stock RC, Catania A, Lipton JM: Evidence of autocrine modulation of macrophage nitric oxide synthase by α-melanocyte-stimulating hormone. Proc Natl Acad Sci USA 1995;92:8016–8020.
  18. Chiao H, Foster S, Thomas R, Lipton J, Star R: α-Melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation. J Clin Invest 1996;97:2038–2044.
  19. Mason MJ, Van Epps D: Modulation of IL-1, tumor necrosis factor, and C5a-mediated murine neutrophil migration by α-melanocyte-stimulating hormone. J Immunol 1989;142:1646–1651.
  20. Catania A, Rajora N, Capsoni F, Minonzio F, Star RA, Lipton JM: The neuropeptide α-MSH has specific receptors on neutrophils and reduces chemotaxis in vitro. Peptides 1996;17:675–679.

    External Resources

  21. Grabbe S, Bhardwaj RS, Mahnke K, Simon MM, Schwarz T Luger TA: α-Melanocyte-stimulating hormone induces hapten-specific tolerance in mice. J Immunol 1996;156:473–478.
  22. Manna SK, Aggarwal BB: α-Melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-κB activation induced by various inflammatory agents. J Immunol 1998;161:2873–2880.
  23. Ichiyama T, Zhao H, Catania A, Furukawa S, Lipton JM: α-Melanocyte-stimulating hormone inhibits NF-κB activation and IκBα degradation in human glioma cells and in experimental brain inflammation. Exp Neurol 1999;157:359–365.
  24. Abdel-Malek ZA: Melanocortin receptors: Their functions and regulation by physiological agonists and antagonists. Cell Mol Life Sci 2001;58:434–441.
  25. Taherzadeh S, Sharma S, Chhajlani V, Gantz I, Rajora N, Demitri MT, Kelly L, Zhao H, Catania A, Lipton JM: α-MSH and its receptors in regulation of inflammatory tumor necrosis factor-α by human monocyte/macrophages. Am J Physiol 1999;276:R1289–R1294.
  26. van der Kraan M, Adan RA, Entwistle ML, Gispen WH, Burbach JP, Tatro JB: Expression of melanocortin-5 receptor in secretory epithelia supports a functional role in exocrine and endocrine glands. Endocrinology 1998;139:2348–2355.
  27. Chen W, Kelly MA, Opitz-Araya X, Thomas RE, Low MJ, Cone RD: Exocrine gland dysfunction in MC5-R-deficient mice: Evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell 1997;91:789–798.
  28. Taylor AW, Namba K: In vitro induction of CD25+ CD4+ regulatory T cells by the neuropeptide α-melanocyte-stimulating hormone (α-MSH). Immunol Cell Biol 2001;79:358–367.
  29. Benjannet S, Rondeau N, Day R, Chrétien M, Seidah NG: PC1 and PC2 are pro-protein convertases capable of cleaving proopiomelanocortin at distinct pairs of basic residues. Proc Natl Acad Sci USA 1991;88:3564–3568.
  30. Taylor A, Streilen J, Cousins S: Identification of α-melanocyte stimulating hormone as a potential immunosuppressive factor in aqueous humor. Curr Eye Res 1992;1:1199–1206.
  31. Rajora N, Boccoli G, Catania A, Lipton JM: α-MSH modulates experimental inflammatory bowel disease. Peptides 1997;18:381–385.
  32. Oktar BK, Ercan F, Yegen BC, Alican I: The effect of α-melanocyte-stimulating hormone on colonic inflammation in the rat. Peptides 2000;21:1271–1277.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50