The Journal of Experimental Medicine
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Published online 21 February 2006 doi:10.1084/jem.20052017
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 3, 563-571
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ARTICLE

 Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia

Elena Gonzalez-Rey, Alejo Chorny, Gema Robledo, and Mario Delgado

Institute of Parasitology and Biomedicine, Consejo Superior de Investigaciones Cientificas, Granada 18100, Spain

CORRESPONDENCE Mario Delgado: mdelgado{at}ipb.csic.es

Cortistatin is a recently discovered cyclic neuropeptide related to somatostatin that has emerged as a potential endogenous antiinflammatory factor based on its production by and binding to immune cells. Because human septic shock involves excessive inflammatory cytokine production, we investigated the effect of cortistatin on the production of inflammatory mediators and its therapeutic action in various murine models of endotoxemia. Cortistatin down-regulated the production of inflammatory mediators by endotoxin-activated macrophages. The administration of cortistatin protected against lethality after cecal ligation and puncture, or injection of bacterial endotoxin or Escherichia coli, and prevented the septic shock-associated histopathology, such as infiltration of inflammatory cells and intravascular disseminated coagulation in various target organs. The therapeutic effect of cortistatin was mediated by decreasing the local and systemic levels of a wide spectrum of inflammatory mediators, including cytokines, chemokines, and acute phase proteins. The combined use of cortistatin and other antiinflammatory peptides was very efficient treating murine septic shock. This work provides the first evidence of cortistatin as a new immunomodulatory factor with the capacity to deactivate the inflammatory response. Cortistatin represents a potential multistep therapeutic agent for human septic shock, to be used in combination with other immunomodulatory agents or as a complement to other therapies.

Abbreviations used: APP, acute phase protein; CLP, cecal ligation and puncture; MPO, myeloperoxidase; NO, nitric oxide; RANTES, regulated on activation, normal T cell expressed and secreted; SAA, serum amyloid A; VIP, vasoactive intestinal peptide.


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