title: Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia.
abstract: Because of its ability to efficiently inhibit in vitro cytokine production by activated macrophages, we hypothesized that interleukin (IL) 10 might be of particular interest in preventing endotoxin-induced toxicity. We therefore examined the effects of IL-10 administration before lipopolysaccharide (LPS) challenge in mice. A marked reduction in the amounts of LPS-induced tumor necrosis factor (TNF) release in the circulation was observed after IL-10 pretreatment at doses at low as 10 U. IL-10 also efficiently prevented the hypothermia generated by the injection of 100 micrograms LPS. Finally, pretreatment with a single injection of 1,000 U IL-10 completely prevented the mortality consecutive to the challenge with 500 micrograms LPS, a dose that was lethal in 50% of the control mice. We conclude that IL-10 inhibits in vivo TNF secretion and protects against the lethality of endotoxin in a murine model of septic shock.
authors.affiliation: Institut de Recherche Interdisciplinaire, Université Libre de Bruxelles, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Gérard
authors.forename: C
authors.initials: C
authors.lastname: Bruyns
authors.forename: A
authors.initials: A
authors.lastname: Marchant
authors.forename: D
authors.initials: D
authors.lastname: Abramowicz
authors.forename: P
authors.initials: P
authors.lastname: Vandenabeele
authors.forename: A
authors.initials: A
authors.lastname: Delvaux
authors.forename: W
authors.initials: W
authors.lastname: Fiers
authors.forename: M
authors.initials: M
authors.lastname: Goldman
authors.forename: T
authors.initials: T
authors.lastname: Velu
mesh_terms: D000818:Animals; D001483:Base Sequence; D004731:Endotoxins / Q000633:toxicity*; D007035:Hypothermia / Q000517:prevention & control; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012636:Secretory Rate / Q000187:drug effects; D012772:Shock, Septic / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10