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The cannabinoid 2 receptor mitigates survival and tissue damage during sepsis
Author(s) -
Caldwell Charles C.,
Tschoep Johannes,
Goetzman Holly S.,
Choi Lisa G.,
Adediran Samuel
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.675.10
Subject(s) - cannabinoid receptor type 2 , sepsis , cannabinoid , cannabinoid receptor , immune system , chemokine , receptor , inflammation , medicine , immunology , endocrinology , chemistry , agonist
Cannabinoids have both psychotropic and immunomodulatory effects. It has been suggested that immune effects are mediated by the cannabinoid 2 receptor (CB2R), which is expressed upon leukocytes. In this study, we obtained CB2R knockout mice (KO) and subjected them to cecal ligation and puncture (CLP) to define the role of this receptor in sepsis. We observed that CB2R KO mice showed a significantly higher mortality as compared to the wild type (WT) control group. CB2 KO mice also showed increased serum IL‐6 levels 6 hours after CLP as compared to the WT group. At 24 hours following CLP: 1) We found a significant increase in bacteremia in CB2R KO mice. 2) The chemokines KC and MIP‐2 were significantly elevated in CB2R KO mice as compared to the WT control. 3) We determined that numbers of neutrophils in septic CB2R KO mice showed a significant increase at the site of infection. 4) Lung bacterial load and the tissue damage were significantly higher in CB2 KO mice as compared to the WT control. 5) Furthermore, CB2R KO mice showed significantly higher blood urea nitrogen as well as increased histological evidence of kidney damage. These data suggest that the CB2R beneficially mediates the immune response during sepsis. This study is funded by NIH R01 GM72760.