Cachectin/tumor necrosis factor: Production, distribution, and metabolic fate in vivo

B. A. Beutler, I. W. Milsark, A. Cerami

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Abstract

A highly specific radioreceptor assay for cachectin/tumor necrosis factor (TNF) was utilized to measure the time course of lipopolysaccharide (LPS)-induced hormone production in rabbits. Cachectin/TNF bioactivity was monitored in the same serum samples by measuring lipoprotein lipase (LPL) suppression in 3T3-L1 cells. Cachectin/TNF is produced in large quantities by LPS-treated rabbits without priming by bacillus Calmette Guerin, C. parvum, or other agents. Nanomolar concentrations of the hormone are achieved, with peak levels occurring at 2 hr postinjection; the hormone is rapidly cleared thereafter. In separate studies, mice were used to assess the distribution and metabolic fate of cachectin/TNF. Radioiodinated hormone is cleared from the plasma with a half-life of 6 to 7 min. Studies of the tissue distribution of label after injection demonstrate that liver, kidneys, skin, and gastrointestinal tract take up most of the hormone. Electrophoretic analysis of tissues recovered from injected animals suggests that the hormone is very rapidly degraded after binding.

Original languageEnglish (US)
Pages (from-to)3972-3977
Number of pages6
JournalJournal of Immunology
Volume135
Issue number6
StatePublished - Dec 1 1985

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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