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Therapeutic effect of cortistatin on experimental arthritis by downregulating inflammatory and Th1 responses
  1. Elena Gonzalez-Rey (elenag{at}ipb.csic.es)
  1. Institute of Parasitology and Biomedicine, CSIC, Spain
    1. Alejo Chorny (achorny{at}ipb.csic.es)
    1. Institute of Parasitology and Biomedicine, CSIC, Spain
      1. Raimundo G. Del Moral
      1. University of Granada, School of Medicine, Spain
        1. Nieves Varela
        1. Institute of Parasitology and Biomedicine, CSIC, Spain
          1. Mario Delgado (mdelgado{at}ipb.csic.es)
          1. Institute of Parasitology and Biomedicine, CSIC, Spain

            Abstract

            Objective: 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. This study proposes a new strategy for the treatment of arthritis based on the administration of cortistatin, a newly discovered neuropeptide with anti-inflammatory actions.

            Methods: DBA/1J mice with collagen-induced arthritis (CIA) were treated with cortistatin after onset of disease, and clinical score and joint histopathology were evaluated. Inflammatory response was determined by measuring the levels of different inflammatory mediators (cytokines and chemokines) in joints and serum. Th1-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with collagen and by assaying the content of serum autoantibodies.

            Results: Cortistatin treatment significantly reduced the severity of established CIA, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of cortistatin was associated with a striking reduction of the two deleterious components of the disease, i.e. the Th1- driven autoimmune and inflammatory responses. Cortistatin downregulated the production of various inflammatory cytokines and chemokines, decreased the antigen-specific Th1-cell expansion, and induced the production of regulatory cytokines, such as IL-10 and TGF1. Cortistatin exerted its effects on synovial cells through both somatostatin- and ghrelin- receptors, showing a higher effect than both peptides protecting against experimental arthritis.

            Conclusion: This work provides a powerful rationale for the assessment of the efficacy of cortistatin as a novel therapeutic approach to the treatment of rheumatoid arthritis.

            • Th1/Th2 cells
            • autoimmunity
            • inflammation
            • neuroimmunology
            • rheumatoid arthritis

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