title: Relative hyperoxia augments lipopolysaccharide-stimulated cytokine secretion by murine macrophages.
abstract: 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.
authors.affiliation: Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Daren S
authors.initials: DS
authors.lastname: Danielson
authors.forename: Wyrta
authors.initials: W
authors.lastname: Heagy
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Nieman
authors.forename: Michael A
authors.initials: MA
authors.lastname: West
mesh_terms: 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
chemical_list: D003470:Culture Media; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen