The cannabinoid receptor 2 is critical for the host response to sepsis

Johannes Tschöp, Kevin R. Kasten, Ruben Nogueiras, Holly S. Goetzman, Cynthia M. Cave, Lisa G. England, Jonathan Dattilo, Alex B. Lentsch, Matthias H. Tschöp, Charles C. Caldwell

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Leukocyte function can be modulated through the cannabinoid receptor 2 (CB2R). Using a cecal ligation and puncture (CLP) model of sepsis, we examined the role of the CB2R during the immune response to an overwhelming infection. CB2R-knock out (KO) mice showed decreased survival as compared with wild-type mice. CB2R-KO mice also had increased serum IL-6 and bacteremia. Twenty-four hours after CLP, the CB2R-deficient mice had increased lung injury. Additionally, CB2R-deficiency led to increased neutrophil recruitment, decreased neutrophil activation, and decreased p38 activity at the site of infection. Consistent with a novel role for CB2R in sepsis, CB2R-agonist treatment in wild-type mice increased the mean survival time in response to CLP. Treatment with CB2R-agonist also decreased serum IL-6 levels, bacteremia, and damage to the lungs compared with vehicle-treated mice. Finally, the CB2R agonist decreased neutrophil recruitment, while increasing neutrophil activation and p38 activity at the site of infection compared with vehicle-treated mice. These data suggest that CB2R is a critical regulator of the immune response to sepsis and may be a novel therapeutic target.

Original languageEnglish
Pages (from-to)499-505
Number of pages7
JournalJournal of Immunology
Volume183
Issue number1
DOIs
StatePublished - 1 Jul 2009
Externally publishedYes

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