The melanocortin peptide HP228 displays protective effects in acute models of inflammation and organ damage.
The clinically efficacious melanocortin peptide HP228 has here been investigated for its anti-inflammatory efficacy. In this study we have investigated the efficacy of HP228 in murine acute models of inflammation and myocardial ischaemia. Systemic treatment of mice with HP228 inhibited neutrophil accumulation in zymosan; urate crystal and carrageenan induced inflammatory models. In the urate model this was due to inhibition of pro-inflammatory chemokines and cytokines, whilst different mechanisms exist for zymosan peritonitis and carrageenan-induced air-pouch inflammation. HP228 was next evaluated in a model of myocardial ischaemia, another condition where cytokines and neutrophils are thought to play a causal role. HP228 caused a 50% reduction in myocardial damage following reperfusion. HP228 therefore inhibits the most important facet of the host inflammatory response namely leukocyte migration. These data show for the first time that the clinically efficacious peptide HP228 displays protective effects in models of inflammation and organ damage.
Getting
Stephen J
SJ
Centre for Biochemical Pharmacology and Experimental Pathology, The William Harvey Research Institute, Bart's and the London SMD, Charterhouse Square, London EC1M 6BQ, UK. S.J.Getting@qmul.ac.uk
Di Filippo
Clara
C
D'Amico
Michele
M
Perretti
Mauro
M
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002351:Carrageenan; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D000242:Cyclic AMP / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007375:Interleukin-1 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D010538:Peritonitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014527:Uric Acid; D015054:Zymosan; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D007375:Interleukin-1; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; C096756:HP 228; C074302:keratinocyte-derived chemokines; D014527:Uric Acid; D000521:alpha-MSH; D002351:Carrageenan; D015054:Zymosan; D000242:Cyclic AMP