KINETICS OF DECREASED LPS-STIMULATED CYTOKINE RELEASE BY MACROPHAGES EXPOSED TO CO2

The mechanisms responsible for the lack of inflammation after laparosc opic surgery remain unknown. Peritoneal macrophages (MO) incubated in carbon dioxide (CO2), but not air or helium (He), had significant, rev ersible inhibition of lipopolysaccharide (LPS)-stimulated tumor necros is factor (TNF) and interleukin-1 (IL-1) release, In these experiments the kinetics of these CO2-induced alterations in cytokine secretion w ere examined. Murine peritoneal MO were stimulated with LPS for 4 hr a nd incubated in different test gases (95% air/5% CO2, 80% CO2/20% O-2, 80% He/20% O-2) for intervals between 0.25 and 4 hr. Time between gas incubation and LPS stimulation was varied to determine the persistenc e of CO2 inhibition. Parallel MO groups received LPS stimulation 24 hr later. Supernatant TNF and IL-1 were measured by bioassay and polymer ase chain reaction was used to examine cytokine mRNA. Significant reve rsible 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 associate d with decreased IL-1 mRNA, and was rapidly lost following incubation in the control atmosphere. TNF inhibition was seen despite normal leve ls of TNF message, required more than 30 min of CO2 exposure, and pers isted after CO2 removal, CO2 produced profound, reversible, inhibition of LPS-stimulated cytokine release by peritoneal MO. The transient in ability to secrete inflammatory cytokines after CO2 exposure may expla in the lack of systemic inflammation after laparoscopic surgery with C O2. (C) 1996 Academic Press, Inc.