Tolerance to tumor necrosis factor in rats and the relationship to endotoxin tolerance and toxicity.

Abstract

Treatment of rats with recombinant human TNF initially causes a marked decrease in food intake, a loss of body weight, and a negative nitrogen balance. These alterations normalize with continued twice daily intraperitoneal injections of the same dose. Rats tolerized to TNF in this manner are refractory to a lethal dose of TNF. Also, TNF-pretreated and -tolerized rats have prolonged survival and reversed histopathologic changes after injection of a lethal dose of endotoxin compared with control animals. The TNF-tolerant state is dependent on the dose of TNF used and the length of TNF pretreatment. TNF-induced tolerance is relatively short lived, being present 2-4 d after TNF pretreatment and dissipating by 2 wk. Rats made tolerant to endotoxin are also tolerant to a lethal dose of TNF. A bidirectional crossreacting tolerance exists between TNF and endotoxin. The mechanism of TNF tolerance is unclear, but it does not appear to be due to a humoral immune response or a perturbation of the uptake and clearance of injected TNF.

• Authors: D L Fraker, M C Stovroff, M J Merino, J A Norton
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 168 Issue 1 Pg. 95-105 (Jul 01 1988) ISSN: 0022-1007 [Print] United States
• PMID: 3294337 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Endotoxins
• Immunoglobulin G
• Immunoglobulin M
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• Nitrogen

Topics

• Animals
• Body Weight
• Drug Tolerance
• Eating
• Endotoxins (pharmacology, toxicity)
• Escherichia coli
• Immunoglobulin G (biosynthesis)
• Immunoglobulin M (biosynthesis)
• Kinetics
• Male
• Nitrogen (metabolism)
• Rats
• Rats, Inbred F344
• Recombinant Proteins (pharmacology)
• Tumor Necrosis Factor-alpha (administration & dosage, immunology, pharmacology)