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(American Journal of Pathology. 2007;170:263-271.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060596

Adrenomedullin Protects from Experimental Arthritis by Down-Regulating Inflammation and Th1 Response and Inducing Regulatory T Cells

Elena Gonzalez-Rey*{dagger}, Alejo Chorny*, Francisco O’Valle{ddagger} and Mario Delgado*

From the Institute of Parasitology and Biomedicine,* Spanish Council of Scientific Research, Granada; the Department of Biochemistry and Molecular Biology,{dagger} Medical School of Seville, Seville; and the Department of Pathology,{ddagger} University of Granada, Granada, Spain

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.






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Copyright © 2007 by the American Society for Investigative Pathology.