title: Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells.
abstract: Exposure to hypoxia (PO2 = 9 +/- 1 torr) increased human peripheral blood mononuclear cell production and secretion of interleukin-1 (IL-1)alpha, IL-1 beta, and tumor necrosis factor (TNF) percent of control = 190% for IL-1 alpha, p = 0.014; 219% for IL-1 beta, p = 0.014; and 243% for TNF, p = 0.037) following treatment with endotoxin (1 ng/ml). Hypoxia potentiated the increased production of these inflammatory cytokines at subthreshold levels of endotoxin with potentiation increasing at lower O2 concentrations. Hypoxia also increased cytokine production induced by the tumor promoter phorbol myristate acetate, suggesting a generalized biologic response. We conclude that hypoxia increases IL-1 and TNF production and speculate that this mechanism aggravates a variety of pathologic conditions involving endotoxin such as adult respiratory distress syndrome (ARDS), multiple organ failure, and septic shock.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ghezzi
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: M
authors.initials: M
authors.lastname: Bianchi
authors.forename: M E
authors.initials: ME
authors.lastname: Rosandich
authors.forename: J E
authors.initials: JE
authors.lastname: Repine
authors.forename: C W
authors.initials: CW
authors.lastname: White
mesh_terms: D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011863:Radioimmunoassay; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D013755:Tetradecanoylphorbol Acetate