title: Adrenomedullin protects from experimental autoimmune encephalomyelitis at multiple levels.
abstract: Adrenomedullin is a neuropeptide known for its cardiovascular activities and anti-inflammatory effects. Here, we investigated the effect of adrenomedullin in a model of experimental autoimmune encephalomyelitis (EAE) that mirrors chronic progressive multiple sclerosis. A short-term systemic treatment with adrenomedullin reduced clinical severity and incidence of EAE, the appearance of inflammatory infiltrates in spinal cord and the subsequent demyelination and axonal damage. This effect was exerted at multiple levels affecting both early and late events of the disease. Adrenomedullin decreased the presence/activation of encephalitogenic Th1 and Th17 cells and down-regulated several inflammatory mediators in peripheral lymphoid organs and central nervous system. Noteworthy, adrenomedullin inhibited the production by encephalitogenic cells of osteopontin and of Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), two critical cytokines in the development of EAE. At the same time, adrenomedullin increased the number of IL-10-producing regulatory T cells with suppressive effects on the progression of EAE. Furthermore, adrenomedullin generated dendritic cells with a semi-mature phenotype that impaired encephalitogenic responses in vitro and in vivo. Finally, adrenomedullin regulated glial activity and favored an active program of neuroprotection/regeneration. Therefore, the use of adrenomedullin emerges as a novel multimodal therapeutic approach to treat chronic progressive multiple sclerosis.
authors: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, Granada, Spain.
authors: Marta
authors: M
authors: Pedreño
authors: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, Granada, Spain.
authors: Maria
authors: M
authors: Morell
authors: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, Granada, Spain.
authors: Gema
authors: G
authors: Robledo
authors: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, Granada, Spain.
authors: Luciana
authors: L
authors: Souza-Moreira
authors: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, Granada, Spain.
authors: Irene
authors: I
authors: Forte-Lago
authors: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, Granada, Spain.
authors: Marta
authors: M
authors: Caro
authors: Dept. Pathological Anatomy, Granada University School of Medicine, Granada, Spain.
authors: Francisco
authors: F
authors: O'Valle
authors: Dept. Immunology and Microbiology, Temple University School of Medicine, Philadelphia, PA, USA.
authors: Doina
authors: D
authors: Ganea
authors: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, Granada, Spain. Electronic address: elenag@ipb.csic.es.
authors: Elena
authors: E
authors: Gonzalez-Rey
mesh_terms: D053607:Adrenomedullin / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; D053607:Adrenomedullin
keywords: Adrenomedullin; Autoimmunity; Dendritic cells; Glial cells; Multiple sclerosis; Neuropeptide; Regulatory T cells