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 c arbon 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 me chanisms involved, the authors investigated the effect of different ga ses on murine peritoneal macrophage intracellular pH and correlated th ese alterations with alterations in LPS-stimulated inflammatory cytoki ne 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 (T NF) and interleukin-l release compared. Cytosolic pH of macrophages ex posed to test gases was measured using single-cell fluorescent imaging . The in vivo effects of test gases were determined in anesthetized ra ts 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, caus ed a marked cytosolic acidification. Pharmacologic induction of intrac ellular acidification to similar levels reproduced the inhibitory effe ct. In vitro studies showed that CO2 insufflation lowered tissue pH an d 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 respon se during laparoscopic surgery.