Protection against rat endotoxic shock by p55 tumor necrosis factor (TNF) receptor immunoadhesin: comparison with anti-TNF monoclonal antibody.

Abstract

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.

• Authors: H Jin, R Yang, S A Marsters, S A Bunting, F M Wurm, S M Chamow, A Ashkenazi
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 170 Issue 5 Pg. 1323-6 (Nov 1994) ISSN: 0022-1899 [Print] United States
• PMID: 7963738 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin G
• Lipopolysaccharides
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Blood Pressure (drug effects)
• Heart Rate (drug effects)
• Immunoglobulin G (therapeutic use)
• Lipopolysaccharides (toxicity)
• Male
• Rats
• Rats, Sprague-Dawley
• Receptors, Tumor Necrosis Factor (physiology)
• Shock, Septic (prevention & control)
• Tumor Necrosis Factor-alpha (physiology)