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PMID: 3294337 Published · ppublish English Comparative Study Journal Article

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

The Journal of experimental medicine ·Vol. 168 ·No. 1 ·1988-07-01 ·Pages 95-105

Fraker DL, Stovroff MC, Merino MJ, Norton JA

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.

MeSH Terms
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
Chemicals
Endotoxins Immunoglobulin G Immunoglobulin M Recombinant Proteins Tumor Necrosis Factor-alpha Nitrogen
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fraker D L
Surgical Metabolism Section, National Cancer Institute, Bethesda, Maryland 20892.
Stovroff M C
Merino M J
Norton J A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.168.1.95
Published
1988-07-01
Pages
95-105
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2188973
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.168.1.95 PMC Full Text View journal details
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