title: The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) therapy.
abstract: The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) plays an important role in immune privilege by its suppression of inflammation, and its induction of regulatory T cells. This finding led us to test the possibility that we can use alpha-MSH to suppress autoimmune diseases, and promote re-establishment of immune tolerance to autoantigens. To test this possibility, SJL mice with experimental autoimmune encephalomyelitis (EAE) were injected with alpha-MSH at the first signs of paralysis. The alpha-MSH-treated mice in comparison with untreated EAE mice had a profound diminishment in the severity and tempo of EAE. The spleen cells in alpha-MSH-treated EAE produced TGF-beta in response to PLP-antigen stimulation in contrast to untreated mice spleen cells that produced IFN-gamma. When the alpha-MSH-treated EAE mice were reimmunized there was a delay of a week before the second episode of EAE. Although this delay maybe because of the induction of TGF-beta-producing spleen cells by the alpha-MSH-treatment, it was not adequate to suppress IFN-gamma-production by PLP-antigen stimulated spleen cells from untreated mice, nor able to suppress the eventual second episode of EAE. Therefore, the injection of alpha-MSH at the onset of paralysis is extremely effective in diminishing the severity and tempo of EAE, and the subsequent induction of potential PLP-specific Treg cells suggests that an alpha-MSH therapy could be attempted as part of a therapeutic regiment to impose immunoregulation and immunosuppression on an autoimmune disease of the central nervous system.
authors.affiliation: Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA. andrew.taylor@schepens.harvard.edu
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Taylor
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kitaichi
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D015213:Neuroimmunomodulation / Q000187:drug effects; D010446:Peptide Fragments / Q000096:biosynthesis; D011510:Proteolipids / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D001324:Autoantigens; D010446:Peptide Fragments; D011510:Proteolipids; D016212:Transforming Growth Factor beta; C104514:interferon-gamma (95-133); D000521:alpha-MSH; D007371:Interferon-gamma