title: CB2 cannabinoid receptors contribute to bacterial invasion and mortality in polymicrobial sepsis.
abstract: BACKGROUND
  Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens. It was recently proposed that endogenous mediators produced during sepsis can contribute to the immune dysfunction that is observed in sepsis. Endocannabinoids that are produced excessively in sepsis are potential factors leading to immune dysfunction, because they suppress immune cell function by binding to G-protein-coupled CB(2) receptors on immune cells. Here we examined the role of CB(2) receptors in regulating the host's response to sepsis.
  
  
  RESULTS
  The role of CB(2) receptors was studied by subjecting CB(2) receptor wild-type and knockout mice to bacterial sepsis induced by cecal ligation and puncture. We report that CB(2) receptor inactivation by knockout decreases sepsis-induced mortality, and bacterial translocation into the bloodstream of septic animals. Furthermore, CB(2) receptor inactivation decreases kidney and muscle injury, suppresses splenic nuclear factor (NF)-kappaB activation, and diminishes the production of IL-10, IL-6 and MIP-2. Finally, CB(2) receptor deficiency prevents apoptosis in lymphoid organs and augments the number of CD11b(+) and CD19(+) cells during CLP.
  
  
  CONCLUSIONS
  Taken together, our results establish for the first time that CB(2) receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2) receptors may be therapeutically targeted for the benefit of patients suffering from sepsis.
authors.affiliation: Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, United States of America.
authors.forename: Balázs
authors.initials: B
authors.lastname: Csóka
authors.forename: Zoltán H
authors.initials: ZH
authors.lastname: Németh
authors.forename: Partha
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Spolarics
authors.forename: Mohanraj
authors.initials: M
authors.lastname: Rajesh
authors.forename: Stephanie
authors.initials: S
authors.lastname: Federici
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
authors.forename: Sándor
authors.initials: S
authors.lastname: Bátkai
authors.forename: Pál
authors.initials: P
authors.lastname: Pacher
authors.forename: György
authors.initials: G
authors.lastname: Haskó
mesh_terms: D000818:Animals; D018407:Bacterial Physiological Phenomena; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043885:Receptor, Cannabinoid, CB2 / Q000502:physiology*; D018805:Sepsis / Q000503:physiopathology*
chemical_list: D016207:Cytokines; D043885:Receptor, Cannabinoid, CB2