title: Mechanism of decreased in vitro murine macrophage cytokine release after exposure to carbon dioxide: relevance to laparoscopic surgery.
abstract: OBJECTIVE
  The objective of this study was to determine the effect of carbon dioxide (CO2) on the function of peritoneal macrophages.
  
  
  BACKGROUND
  Laparoscopic surgery is associated with minimal pain, fever, and low levels of inflammatory cytokines. To understand the mechanisms involved, the authors investigated the effect of different gases on murine peritoneal macrophage intracellular pH and correlated these alterations with alterations in LPS-stimulated inflammatory cytokine release.
  
  
  METHODS
  Peritoneal macrophages were incubated for 2 hours in air, helium, or CO2, and the effect of the test gas on immediate or next day lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) and interleukin-1 release compared. Cytosolic pH of macrophages exposed to test gases was measured using single-cell fluorescent imaging. The in vivo effects of test gases were determined in anesthetized rats during abdominal insufflation.
  
  
  RESULTS
  Macrophages incubated in CO2 produced significantly less TNF and interleukin-1 in response to LPS compared to incubation in air or helium. Cytokine production returned to normal 24 hours later. Exposure to CO2, but not air or helium, caused a marked cytosolic acidification. Pharmacologic induction of intracellular acidification to similar levels reproduced the inhibitory effect. In vitro studies showed that CO2 insufflation lowered tissue pH and peritoneal macrophage LPS-stimulated TNF production.
  
  
  CONCLUSIONS
  The authors propose that cellular acidification induced by peritoneal CO2 insufflation contributes to blunting of the local inflammatory response during laparoscopic surgery.
authors.affiliation: Department of Surgery, Hennepin County Medical Center University of Minnesota, Minneapolis 55415, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: West
authors.forename: D J
authors.initials: DJ
authors.lastname: Hackam
authors.forename: J
authors.initials: J
authors.lastname: Baker
authors.forename: J L
authors.initials: JL
authors.lastname: Rodriguez
authors.forename: J
authors.initials: J
authors.lastname: Bellingham
authors.forename: O D
authors.initials: OD
authors.lastname: Rotstein
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007375:Interleukin-1 / Q000378:metabolism*; D010535:Laparoscopy; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide