The cannabinoid receptor 2 is critical for the host response to sepsis.
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.
Tschöp
Johannes
J
Department of Surgery, University of Cincinnati College of Medicine, OH 45267, USA.
Kasten
Kevin R
KR
Nogueiras
Ruben
R
Goetzman
Holly S
HS
Cave
Cynthia M
CM
England
Lisa G
LG
Dattilo
Jonathan
J
Lentsch
Alex B
AB
Tschöp
Matthias H
MH
Caldwell
Charles C
CC
D000818:Animals; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D002432:Cecum; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D039421:Integrin alpha2 / Q000008:administration & dosage / Q000627:therapeutic use; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D011677:Punctures; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012772:Shock, Septic / Q000276:immunology* / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D018836:Inflammation Mediators; D039421:Integrin alpha2; D043885:Receptor, Cannabinoid, CB2