Adrenomedullin protects from experimental arthritis by down-regulating inflammation and Th1 response and inducing regulatory T cells.
Rheumatoid arthritis is a chronic autoimmune disease of unknown etiology characterized by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. The present study proposes a new strategy for the treatment of arthritis: the administration of the immunomodulatory neuropeptide adrenomedullin. Treatment with adrenomedullin significantly reduced incidence and severity of collagen-induced arthritis, an experimental model of rheumatoid arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of adrenomedullin was associated with a striking reduction of the two deleterious components of the disease, ie, the Th1-driven autoimmune and inflammatory responses. Adrenomedullin also induced the generation and/or activation of efficient CD4+ CD25+ regulatory T cells in arthritis with capacity to suppress autoreactive response and restore immune tolerance, which could play a pivotal role in the therapeutic effect of adrenomedullin on experimental arthritis contributing to the restoration of immune tolerance.
Gonzalez-Rey
Elena
E
Institute of Parasitology and Biomedicine, Spanish Council of Scientific Research, Granada, Spain. elenag@ipb.csic.es
Chorny
Alejo
A
O'Valle
Francisco
F
Delgado
Mario
M
D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control*; D015551:Autoimmunity; D024043:Collagen Type II; D015536:Down-Regulation / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology; D007249:Inflammation; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D024043:Collagen Type II; D007155:Immunologic Factors; D053607:Adrenomedullin