Background. α-Melanocyte stimulating hormone (α-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. Materials and methods. Effects of (CKPV)2, KPV, and [Nle4-dPhe7]-α-MSH (NDP-α-MSH) on tumor necrosis factor α (TNF-α) 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 (NO 2-) and TNF-α were measured in blood and peritoneal fluid at 7 h. Results. (CKPV)2 inhibited TNF-α production by LPS-stimulated human PBMC. This small peptide was as effective as NDP-α-MSH and more potent than KPV. Similar effectiveness was observed in vivo: 1 h after LPS injection, the large increase in circulating TNF-α 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-α and NO2 - both in plasma and in dialysate. Conclusions. The remarkable capacity of (CKPV)2 to inhibit endotoxin-induced host reactions suggests that it may be useful in treatment of inflammatory disorders.
Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions / S. Gatti, A. Carlin, A. Sordi, P. Leonardi, G. Colombo, L.R. Fassati, J.M. Lipton, A. Catania. - In: JOURNAL OF SURGICAL RESEARCH. - ISSN 0022-4804. - 131:2(2006 Apr), pp. 209-214.
|Titolo:||Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions|
GATTI, STEFANO (Primo)
CARLIN, ANDREA (Secondo)
|Parole Chiave:||Animals ; Cell Culture Techniques ; Leukocytes, Mononuclear ; Lipopolysaccharides ; Nitric Oxide ; Peptide Fragments ; Peritoneal Dialysis ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; alpha-MSH|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||apr-2006|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jss.2005.08.009|
|Appare nelle tipologie:||01 - Articolo su periodico|