Therapeutic action of ghrelin in a mouse model of colitis.
OBJECTIVE
Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis.


METHODS
We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Diverse clinical signs of the disease were evaluated, including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of ghrelin, such as inflammatory cytokines and chemokines, Th1-type response, and regulatory factors.


RESULTS
Ghrelin ameliorated significantly the clinical and histopathologic severity of the trinitrobenzene sulfonic acid-induced colitis; abrogating body weight loss, diarrhea, and inflammation; and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response through the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of interluekin-10/transforming growth factor-beta1-secreting regulatory T cells in this therapeutic effect was demonstrated. Importantly, the ghrelin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease.


CONCLUSIONS
Our data demonstrate novel anti-inflammatory actions for ghrelin in the gastrointestinal tract, ie, the capacity to deactivate the intestinal inflammatory response and to restore mucosal immune tolerance at multiple levels. Consequently, ghrelin administration represents a novel possible therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis.
Gonzalez-Rey
Elena
E
Institute of Parasitology and Biomedicine, CSIC, Granada, Spain.
Chorny
Alejo
A
Delgado
Mario
M
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D054439:Ghrelin; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis; D007377:Interleukin-3 / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D036361:Peptide Hormones / Q000494:pharmacology*; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000235:genetics; D011994:Recombinant Proteins; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D015415:Biomarkers; D054439:Ghrelin; D018836:Inflammation Mediators; D007377:Interleukin-3; D036361:Peptide Hormones; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C404145:myelopoietin; D016179:Granulocyte Colony-Stimulating Factor