Kinetics of decreased LPS-stimulated cytokine release by macrophages exposed to CO2

Abstract

The mechanisms responsible for the lack of inflammation after laparoscopic surgery remain unknown. Peritoneal macrophages (M phi) incubated in carbon dioxide (CO2) but not air or helium (He), had significant, reversible inhibition of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) and interleukin-1 (IL-1) release. In these experiments the kinetics of these C02-induced alterations in cytokine secretion were examined. Murine peritoneal Mphi were stimulated with LPS for 4 hr and incubated in different test gases (95% air/5% CO2,80%CO2/20%O2,80% He/20% O2) for intervals between 0.25 and 4 hr. Time between gas incubation and LPS stimulation was varied to determine the persistence of CO2 inhibition. Parallel M phi groups received LPS stimulation 24 hr later. Supernatant TNF and IL-1 were measured by bioassay and polymerase chain reaction was used to examine cytokine mRNA. Significant reversible inhibition of TNF and IL-1 was seen with CO2, but not He or air. Inhibition of IL-1 occurred 15 min after CO2 exposure, was associated with decreased IL-1 mRNA, and was rapidly lost following incubation in the control atmosphere. TNF inhibition was seen despite normal levels of TNF message, required more than 30 min of CO2 exposure, and persisted after CO2 removal. CO2 produced profound, reversible, inhibition of LPS-stimulated cytokine release by peritoneal Mphi. The transient inability to secrete inflammatory cytokines after CO2 exposure may explain the lack of systemic inflammation after laparoscopic surgery with CO2.