Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions

Stefano Gatti, Andrea Carlin, Andrea Sordi, Patrizia Leonardi, Gualtiero Colombo, Luigi R. Fassati, James M. Lipton, Anna Catania

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)209-214
Number of pages6
JournalJournal of Surgical Research
Volume131
Issue number2
DOIs
Publication statusPublished - Apr 2006

Fingerprint

Endotoxins
Lipopolysaccharides
Melanocyte-Stimulating Hormones
Peptides
MSH (11-13)
Peritonitis
cysteinylcysteine
Dialysis
Blood Cells
Ascitic Fluid
Dialysis Solutions
Nitrites
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Injections
Therapeutics
Research
In Vitro Techniques

Keywords

  • α-Melanocyte stimulating hormone (α-MSH)
  • Endotoxin
  • Nitric oxide (NO)
  • Peritoneal dialysis
  • Peritonitis
  • Synthetic melanocortins
  • Tumor necrosis factor α (TNF-α)

ASJC Scopus subject areas

  • Surgery

Cite this

Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions. / Gatti, Stefano; Carlin, Andrea; Sordi, Andrea; Leonardi, Patrizia; Colombo, Gualtiero; Fassati, Luigi R.; Lipton, James M.; Catania, Anna.

In: Journal of Surgical Research, Vol. 131, No. 2, 04.2006, p. 209-214.

Research output: Contribution to journalArticle

Gatti, S, Carlin, A, Sordi, A, Leonardi, P, Colombo, G, Fassati, LR, Lipton, JM & Catania, A 2006, 'Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions', Journal of Surgical Research, vol. 131, no. 2, pp. 209-214. https://doi.org/10.1016/j.jss.2005.08.009
Gatti, Stefano ; Carlin, Andrea ; Sordi, Andrea ; Leonardi, Patrizia ; Colombo, Gualtiero ; Fassati, Luigi R. ; Lipton, James M. ; Catania, Anna. / Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions. In: Journal of Surgical Research. 2006 ; Vol. 131, No. 2. pp. 209-214.
@article{b8ad1b4cd1304bb0a2696956112f6f75,
title = "Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions",
abstract = "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.",
keywords = "α-Melanocyte stimulating hormone (α-MSH), Endotoxin, Nitric oxide (NO), Peritoneal dialysis, Peritonitis, Synthetic melanocortins, Tumor necrosis factor α (TNF-α)",
author = "Stefano Gatti and Andrea Carlin and Andrea Sordi and Patrizia Leonardi and Gualtiero Colombo and Fassati, {Luigi R.} and Lipton, {James M.} and Anna Catania",
year = "2006",
month = "4",
doi = "10.1016/j.jss.2005.08.009",
language = "English",
volume = "131",
pages = "209--214",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions

AU - Gatti, Stefano

AU - Carlin, Andrea

AU - Sordi, Andrea

AU - Leonardi, Patrizia

AU - Colombo, Gualtiero

AU - Fassati, Luigi R.

AU - Lipton, James M.

AU - Catania, Anna

PY - 2006/4

Y1 - 2006/4

N2 - 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.

AB - 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.

KW - α-Melanocyte stimulating hormone (α-MSH)

KW - Endotoxin

KW - Nitric oxide (NO)

KW - Peritoneal dialysis

KW - Peritonitis

KW - Synthetic melanocortins

KW - Tumor necrosis factor α (TNF-α)

UR - http://www.scopus.com/inward/record.url?scp=33644920663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644920663&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2005.08.009

DO - 10.1016/j.jss.2005.08.009

M3 - Article

C2 - 16413580

AN - SCOPUS:33644920663

VL - 131

SP - 209

EP - 214

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 2

ER -