Tumor necrosis factor α stimulates leukotriene production in vivo

M. Huber, B. Beutler, D. Keppler

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Tumor necrosis factor α, or cachectin (TNF), is a polypeptide mediator with proinflammatory and antitumor actions. It is produced in large amounts by lipopolysaccharide (LPS)-activated macrophages. TNF as well as LPS stimulated the arachidonate cascade leading to the synthesis of leukotrienes (LT) in vivo. Production of endogenous cysteinyl LT was measured in anesthetized rat using the biliary excretion of N-acetyl-LTE4 as an indicator. Infusion of TNF over a 1-h period greatly increased the rate of cysteinyl LT production during the subsequent 3 h. Pretreatment with anti-TNF antibody F(ab')2 fragments prevented enhanced LT generation as well as tachypnea (a sign of the in vivo action of TNF). LT production elicited by TNF was similar to that evoked by infusion of LPS. Our results indicate that lipoxygenase products are involved in the network of pathophysiological events induced by TNF. The proinflammatory and shock-inducing LT may mediate many of the adverse effects of TNF in vivo as well as its antitumor action.

Original languageEnglish (US)
Pages (from-to)2085-2088
Number of pages4
JournalEuropean Journal of Immunology
Volume18
Issue number12
StatePublished - 1988

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Leukotrienes
Tumor Necrosis Factor-alpha
Lipopolysaccharides
Leukotriene E4
Tachypnea
Lipoxygenase
Anti-Idiotypic Antibodies
Shock
Macrophages
Peptides
cysteinyl-leukotriene

ASJC Scopus subject areas

  • Immunology

Cite this

Tumor necrosis factor α stimulates leukotriene production in vivo. / Huber, M.; Beutler, B.; Keppler, D.

In: European Journal of Immunology, Vol. 18, No. 12, 1988, p. 2085-2088.

Research output: Contribution to journalArticle

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