Cortistatin, an antiinflammatory peptide with therapeutic action in inflammatory bowel disease.
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. Crohn's disease is a chronic debilitating disease characterized by severe T helper 1 (Th1)-driven inflammation of the gastrointestinal tract. The aim of this study is to investigate the therapeutic effect of cortistatin in a murine model of colitis. Cortistatin treatment significantly ameliorated the clinical and histopathologic severity of the inflammatory colitis, abrogating body weight loss, diarrhea, and inflammation and increased the survival rate of the colitic mice. The therapeutic effect was associated with down-regulation of inflammatory and Th1-driven autoimmune response, including the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of regulatory IL-10-secreting T cells in this therapeutic effect was demonstrated. Importantly, cortistatin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. This work identifies cortistatin as an antiinflammatory factor with the capacity to deactivate the intestinal inflammatory response and restore mucosal immune tolerance at multiple levels. Consequently, cortistatin represents a multistep therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases.
Institute of Parasitology and Biomedicine, Consejo Superior de Investigaciones Científicas, 18100 Granada, Spain.
Elena
E
Gonzalez-Rey
Nieves
N
Varela
Amir F
AF
Sheibanie
Alejo
A
Chorny
Doina
D
Ganea
Mario
M
Delgado
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009479:Neuropeptides / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D018836:Inflammation Mediators; D009479:Neuropeptides; C099323:cortistatin; D014302:Trinitrobenzenesulfonic Acid