Relative hyperoxia augments lipopolysaccharide-stimulated cytokine secretion by murine macrophages.
BACKGROUND
Increased systemic levels of inflammatory mediators are seen after open abdominal operations. Macrophages that are exposed to lipopolysaccharide secrete cytokines. Peritoneal macrophages normally reside in a pO(2) of 40 mm Hg. We hypothesize that exposure of lipopolysaccharide-stimulated macrophages to "non-physiologic" pO(2) augments cytokine secretion.


METHODS
Murine macrophages were preconditioned to a pO(2) of 40 mm Hg for 24 hours. The medium then was discarded and exchanged for a medium containing a pO(2) of 40, 150, or 440 mm Hg. Macrophages were incubated in the desired pO(2) for 6 and 24 hours while stimulated with lipopolysaccharide (0 to 100 ng/mL). The effect of pO(2) was compared. Supernatant tumor necrosis factor (TNF) and interleukin-6 were measured with enzyme-linked immunosorbent assay. Statistics were performed with analysis of variance.


RESULTS
We found dose-dependent lipopolysaccharide-stimulated TNF and interleukin-6 production with macrophages incubated at physiologic pO(2). Higher pO(2) did not stimulate TNF and interleukin-6 in the absence of lipopolysaccharide. However, a pO(2) of 150 and 440 mm Hg significantly (P <.05) increased lipopolysaccharide-stimulated TNF and interleukin-6 production versus 45 mm Hg.


CONCLUSIONS
Our data suggest synergy between increased pO(2) and lipopolysaccharide for macrophage TNF and interleukin-6 production. Similar pO(2) elevations may occur with an open peritoneum or high supplemental O(2). Cytokines from peritoneal macrophages may contribute to the increased systemic inflammation after open operations.
Danielson
Daren S
DS
Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Heagy
Wyrta
W
Nieman
Kimberly M
KM
West
Michael A
MA
D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018496:Hyperoxia / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D003470:Culture Media; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen