Recombinant soluble tumor necrosis factor receptor proteins protect mice from lipopolysaccharide-induced lethality.
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.
Lesslauer
W
W
F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Tabuchi
H
H
Gentz
R
R
Brockhaus
M
M
Schlaeger
E J
EJ
Grau
G
G
Piguet
P F
PF
Pointaire
P
P
Vassalli
P
P
Loetscher
H
H
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
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