title: Recombinant soluble tumor necrosis factor receptor proteins protect mice from lipopolysaccharide-induced lethality.
abstract: The in vivo efficacy of human recombinant soluble tumor necrosis factor (TNF) receptor protein to prevent and to treat lipopolysaccharide (LPS)-induced lethal toxicity in D-galactosamine-treated mice was investigated. Chimeric proteins of the receptor extracellular domains fused to the hinge region of human IgG3 were expressed in myeloma cells (rsTNFR-h gamma 3). The fusion proteins had a disulfide-bonded dimeric structure. Upon intravenous injection, their serum concentration decreased relatively slowly after an initial phase of rapid elimination. D-galactosamine-sensitized mice were fully protected from the toxic effects of LPS, if the animal were pretreated with rsTNFR-h gamma 3 at 20 micrograms/animal. Partial protection was seen at significantly lower doses and when rsTNFR-h gamma 3 was given up to 3 h after LPS.
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Lesslauer
authors.forename: H
authors.initials: H
authors.lastname: Tabuchi
authors.forename: R
authors.initials: R
authors.lastname: Gentz
authors.forename: M
authors.initials: M
authors.lastname: Brockhaus
authors.forename: E J
authors.initials: EJ
authors.lastname: Schlaeger
authors.forename: G
authors.initials: G
authors.lastname: Grau
authors.forename: P F
authors.initials: PF
authors.lastname: Piguet
authors.forename: P
authors.initials: P
authors.lastname: Pointaire
authors.forename: P
authors.initials: P
authors.lastname: Vassalli
authors.forename: H
authors.initials: H
authors.lastname: Loetscher
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D007074:Immunoglobulin G / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D012772:Shock, Septic / Q000517:prevention & control*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha
chemical_list: D004731:Endotoxins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha