Mechanism of decreased in vitro murine macrophage cytokine release after exposure to carbon dioxide: Relevance to laparoscopic surgery

Objective: The objective of this study was to determine the effect of carbon dioxide (CO₂) on the function of peritoneal macrophages. Summary Background Data: 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.