title: Lipopolysaccharide- and superantigen-modulated superoxide production and monocyte hyporesponsiveness to activating stimuli in sepsis.
abstract: The effects of acute and prior exposure to lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB) on superoxide release by monocytes were examined in control subjects and in patients with sepsis and septic shock during the acute stage and recovery. High doses of LPS, PMA (phorbol 12-myristate 13-acetate), and SEB stimulated monocyte superoxide release in control subjects (P < 0.05). Pretreatment of normal monocytes with these doses of LPS, PMA, and SEB induced significant hyporesponsiveness to subsequent challenge (P < 0.01), and evidence of cross-tolerance was observed. Monocytes isolated from patients with sepsis and septic shock demonstrated high spontaneous superoxide release compared with those of control subjects (P < 0.05). Stimulation of patient monocytes with LPS or SEB resulted in less superoxide production than that spontaneously released by controls (P < 0.01). In patients recovering from their initial infection, spontaneous superoxide release was less than that released during acute stage. In addition, the superoxide release in response to the same stimuli was significantly increased when compared with release during the acute stage (P < 0.05). These data demonstrate that both LPS and SEB induce hyporesponsiveness to LPS- or SEB-stimulated superoxide release. A similar pattern of hyporesponsiveness was observed during sepsis that may represent a mechanism for modulating the inflammatory response during severe infections.
authors.affiliation: Department of Medicine, New York Medical College, Valhalla, New York, USA. Dhanonjoy.Saha@Carolinas.org
authors.forename: Dhanonjoy C
authors.initials: DC
authors.lastname: Saha
authors.forename: Mark E
authors.initials: ME
authors.lastname: Astiz
authors.forename: Lesley-Jane
authors.initials: LJ
authors.lastname: Eales-Reynolds
authors.forename: Eric C
authors.initials: EC
authors.lastname: Rackow
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate
chemical_list: D004768:Enterotoxins; D008070:Lipopolysaccharides; D018089:Superantigens; D013481:Superoxides; C031818:enterotoxin B, staphylococcal; D013755:Tetradecanoylphorbol Acetate