Protection against rat endotoxic shock by p55 tumor necrosis factor (TNF) receptor immunoadhesin: comparison with anti-TNF monoclonal antibody.
The protective efficacy of a p55 tumor necrosis factor receptor immunoadhesin (TNFR-IgG) was compared with that of an anti-TNF monoclonal antibody (MAb) in a rat endotoxic shock model. TNFR-IgG (5 mg/kg), given 30 min before endotoxin (LPS), attenuated LPS induction of hypotension and tachycardia and eliminated LPS induction of serum TNF activity. In contrast, anti-TNF MAb (5 mg/kg) had little effect on LPS-induced hemodynamic changes and neutralized only partially the excessive serum TNF activity. The 6-day survival was 1 of 10 controls; 6 of 11, 5 of 7, and 8 of 9 rats receiving 0.2, 1.0, or 5.0 mg/kg TNFR-IgG, respectively; and 3 of 8 rats receiving 5 mg/kg anti-TNF MAb. These results indicate that TNFR-IgG is more potent than anti-TNF MAb at neutralizing excessive TNF activity in vivo.
Jin
H
H
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.
Yang
R
R
Marsters
S A
SA
Bunting
S A
SA
Wurm
F M
FM
Chamow
S M
SM
Ashkenazi
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D012772:Shock, Septic / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha