Adrenomedullin protects from experimental arthritis by down-regulating inflammation and Th1 response and inducing regulatory T cells.

Abstract

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.

• Authors: Elena Gonzalez-Rey, Alejo Chorny, Francisco O'Valle, Mario Delgado
• Journal: The American journal of pathology (Am J Pathol) Vol. 170 Issue 1 Pg. 263-71 (Jan 2007) ISSN: 0002-9440 [Print] United States
• PMID: 17200199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type II
• Immunologic Factors
• Adrenomedullin

Topics

• Adrenomedullin (pharmacology)
• Animals
• Arthritis, Experimental (immunology, prevention & control)
• Autoimmunity
• Collagen Type II
• Down-Regulation (drug effects)
• Immunologic Factors (pharmacology)
• Inflammation
• Lymphocyte Activation (drug effects)
• Mice
• T-Lymphocyte Subsets (immunology)
• Th1 Cells (immunology)