Format

Send to:

Choose Destination
See comment in PubMed Commons below
Crit Care. 2010;14(5):R187. doi: 10.1186/cc9295. Epub 2010 Oct 7.

Inhibition of monocyte chemoattractant protein-1 prevents diaphragmatic inflammation and maintains contractile function during endotoxemia.

Author information

  • 1Meakins-Christie Laboratories, McGill University, 3626 Saint Urbain, Montreal, Quebec, Canada. katherine.labbe@mail.mcgill.ca

Abstract

INTRODUCTION:

Respiratory muscle weakness is common in sepsis patients. Proinflammatory mediators produced during sepsis have been implicated in diaphragmatic contractile dysfunction, but the role of chemokines has not been explored. This study addressed the role of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), in the pathogenesis of diaphragmatic inflammation and weakness during endotoxemia.

METHODS:

Mice were treated as follows (n = 6 per group): (a) saline, (b) endotoxin (25 μg/g IP), (c) endotoxin + anti-MCP-1 antibody, and (d) endotoxin + isotype control antibody. Muscles were also exposed to recombinant MCP-1 in vivo and in vitro. Measurements were made of diaphragmatic force generation, leukocyte infiltration, and proinflammatory mediator (MCP-1, IL-1α, IL-1β, IL-6, NF-κB) expression/activity.

RESULTS:

In vivo, endotoxin-treated mice showed a large decrease in diaphragmatic force, together with upregulation of MCP-1 and other cytokines, but without an increase in intramuscular leukocytes. Antibody neutralization of MCP-1 prevented the endotoxin-induced force loss and reduced expression of MCP-1, IL-1α, IL-1β, and IL-6 in the diaphragm. MCP-1 treatment of nonseptic muscles also led to contractile weakness, and MCP-1 stimulated its own transcription independent of NF-κB activation in vitro.

CONCLUSIONS:

These results suggest that MCP-1 plays an important role in the pathogenesis of diaphragmatic weakness during sepsis by both direct and indirect mechanisms. We speculate that its immunomodulatory properties and ability to modify skeletal muscle function make MCP-1 a potential therapeutic target in critically ill patients with sepsis and associated respiratory muscle weakness.

PMID:
20950459
[PubMed - indexed for MEDLINE]
PMCID:
PMC3219293
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Write to the Help Desk