Cortistatin, an antiinflammatory peptide with therapeutic action in inflammatory bowel disease

Abstract

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.autoimmunity ͉ cytokines ͉ inflammation ͉ neuroimmunology

The role of cortistatin in the human immune system

“…CST is exerting its therapeutic effect on collagen induced arthritis partially through the ghrelin receptor, which can be partially reversed by a ghrelin-receptor antagonist (Gonzalez-Rey et al, 2007). In two other models studied by the group of Delgado, an experimental inflammatory bowel disease model and a sepsis model, treatment with CST demonstrates clinical and pathological amelioration of disease (Gonzalez-Rey et al, 2006a;Gonzalez-Rey et al, 2006b). These models show the downregulation of the Th1 response and the increase of regulatory T cells that are responsible for the recovery of the immune tolerance.…”

Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages

“…In addition, cortistatin-14 was proposed recently as an alternative ligand for SRIF receptors in the immune system and as a new immunomodulatory factor with the capacity to deactivate the inflammatory response [19]. Recent studies reported a possible therapeutic action of cortistatin-14 in inflammatory bowel disease and septic shock, as assessed in murine models of colitis or endotoxemia [20,63].…”

The Proinflammatory Effect of Prostaglandin E2 in Experimental Inflammatory Bowel Disease Is Mediated through the IL-23→IL-17 Axis

“…A total of 50 mg/ml colon tissue was homogenized and the MPO activity was measured as described previously (40). MPO activity was expressed as units per gram of tissue.…”

“…The detection limits are 15 pg/ml for IL-17, IL-6, IL-12p40, IL-4, IL-10, and IL-23, 30 pg/ml for IFN-␥ and IL-12p70, 7.8 pg/ml for IL-27p28, and 5 pg/ml for TNF. For measurement of tissue cytokines, colonic tissue was processed as previously described (40) and cytokine content was determined by ELISA.…”