Study summary · research use only
Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study, the authors evaluated the peptide (CKPV)2, a dimer of the alpha-MSH C-terminal tripeptide KPV, on endotoxin-induced reactions in human peripheral blood mononuclear cells (PBMC) and in rats. They report that (CKPV)2 inhibited tumor necrosis factor alpha (TNF-alpha) production by lipopolysaccharide-stimulated human PBMC, being comparable to NDP-alpha-MSH and more potent than KPV, and that in rats given lipopolysaccharide it markedly reduced circulating TNF-alpha one hour after injection. In lipopolysaccharide-induced peritonitis, (CKPV)2 restored net ultrafiltrate to control values and lowered TNF-alpha and nitrite in plasma and dialysate. The authors suggest it may be useful in inflammatory disorders.
Abstract
alpha-Melanocyte stimulating hormone (alpha-MSH) is an endogenous peptide that has remarkable anti-inflammatory and antimicrobial effects. These activities have been traced to the C-terminal tripeptide Lys-Pro-Val (KPV). A dimer composed of two KPV sequences connected with a Cys-Cys linker, (CKPV)2, is currently under clinical investigation for antimicrobial use. The present research was designed to evaluate effects of (CKPV)(2) on endotoxin-induced host reactions in vitro and in vivo. Effects of (CKPV)2, KPV, and [Nle4-dPhe7]-alpha-MSH (NDP-alpha-MSH) on tumor necrosis factor alpha (TNF-alpha) production were determined: 1) in human peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide (LPS) in vitro, and 2) in rats injected with LPS i.v. and sacrificed at 1 h. In additional experiments, dialysis peritonitis was induced in rats by adding LPS to dialysis fluid. Net ultrafiltrate was calculated and concentrations of nitrite (NO2-) and TNF-alpha were measured in blood and peritoneal fluid at 7 h. (CKPV)2 inhibited TNF-alpha production by LPS-stimulated human PBMC. This small peptide was as effective as NDP-alpha-MSH and more potent than KPV. Similar effectiveness was observed in vivo: 1 h after LPS injection, the large increase in circulating TNF-alpha was markedly reduced by (CKPV)2 treatment. In LPS-induced peritonitis, (CKPV)2 restored net ultrafiltrate to control values and significantly inhibited concentrations of TNF-alpha and NO2- both in plasma and in dialysate. The remarkable capacity of (CKPV)2 to inhibit endotoxin-induced host reactions suggests that it may be useful in treatment of inflammatory disorders.
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