title: Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease.
abstract: BACKGROUND
  Despite some progress in recent years, the options for treating inflammatory bowel disease (IBD) are still dissatisfying, and surgery rates are still high. The anti-inflammatory effects of melanocortin peptides such as alpha-melanocyte-stimulating hormone (alpha-MSH) have been described recently in, for example, dextran sodium sulfate (DSS) colitis in mice. The aim of this study was to investigate the therapeutic potential of the melanocortin-derived tripeptide alpha-MSH(11-13) (KPV) and its mode of action in 2 models of intestinal inflammation.
  
  
  METHODS
  The anti-inflammatory activity of KPV was analyzed in 2 well-described models of IBD: DSS colitis, and CD45RB(hi) transfer colitis. Furthermore, animals expressing a nonfunctional melanocortin-1 receptor (MC1Re/e) received DSS for induction of colitis and were treated with KPV. The course of inflammation was monitored by weight loss and histological changes in the colon as well as by myeloperoxidase (MPO) activity.
  
  
  RESULTS
  In the DSS-colitis model, treatment with KPV led to earlier recovery and significantly stronger regain of body weight. Histologically, inflammatory infiltrates were significantly reduced in KPV-treated mice, which was confirmed by the significant reduction of MPO activity in colonic tissue after KPV treatment. Supporting these findings, KPV treatment of transfer colitis led to recovery, regain of body weight, and reduced inflammatory changes histologically. In MC1Re/e mice, KPV treatment rescued all animals in the treatment group from death during DSS colitis.
  
  
  CONCLUSIONS
  The melanocortin-derived tripeptide KPV showed significant anti-inflammatory effects in 2 murine models of colitis. These effects seem to be at least partially independent of MC1R signaling. In conclusion, our data suggest KPV as an interesting therapeutic option for the treatment of IBD.
authors: Department of Medicine B, University of Muenster, Muenster, Germany. christian.maaser@klinikum-lueneburg.de
authors: Klaus
authors: K
authors: Kannengiesser
authors: Christian
authors: C
authors: Maaser
authors: Jan
authors: J
authors: Heidemann
authors: Andreas
authors: A
authors: Luegering
authors: Matthias
authors: M
authors: Ross
authors: Thomas
authors: T
authors: Brzoska
authors: Markus
authors: M
authors: Bohm
authors: Thomas A
authors: TA
authors: Luger
authors: Wolfram
authors: W
authors: Domschke
authors: Torsten
authors: T
authors: Kucharzik
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D006728:Hormones / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D044102:Receptor, Melanocortin, Type 1 / Q000096:biosynthesis; D000521:alpha-MSH / Q000627:therapeutic use*
chemical_list: D006728:Hormones; D044102:Receptor, Melanocortin, Type 1; D000521:alpha-MSH; D016264:Dextran Sulfate; D009195:Peroxidase; D017493:Leukocyte Common Antigens