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

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.

• Authors: 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
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 183 Issue 1 Pg. 499-505 (Jul 01 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19525393 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Integrin alpha2
• Receptor, Cannabinoid, CB2

Topics

• Animals
• Bacteremia (immunology, microbiology, mortality, pathology)
• Cecum
• Disease Models, Animal
• Immunity, Innate (genetics)
• Inflammation Mediators (metabolism, physiology)
• Integrin alpha2 (administration & dosage, therapeutic use)
• Ligation
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophil Infiltration (genetics, immunology)
• Punctures
• Receptor, Cannabinoid, CB2 (agonists, deficiency, genetics, physiology)
• Shock, Septic (immunology, microbiology, mortality, pathology)
• Signal Transduction (genetics, immunology)