Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease.
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.
Kannengiesser
Klaus
K
Department of Medicine B, University of Muenster, Muenster, Germany. christian.maaser@klinikum-lueneburg.de
Maaser
Christian
C
Heidemann
Jan
J
Luegering
Andreas
A
Ross
Matthias
M
Brzoska
Thomas
T
Bohm
Markus
M
Luger
Thomas A
TA
Domschke
Wolfram
W
Kucharzik
Torsten
T
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*
D006728:Hormones; D044102:Receptor, Melanocortin, Type 1; D000521:alpha-MSH; D016264:Dextran Sulfate; D009195:Peroxidase; D017493:Leukocyte Common Antigens