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Tumor necrosis factor α stimulates leukotriene production in vivo
Author(s) -
Huber Michael,
Beutler Bruce,
Keppler Dietrich
Publication year - 1988
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830181233
Subject(s) - tumor necrosis factor alpha , proinflammatory cytokine , in vivo , lipopolysaccharide , biology , leukotriene b4 , endocrinology , pharmacology , medicine , immunology , inflammation , microbiology and biotechnology
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‐LTE 4 as an indicator. Infusion of TNF over a 1‐h period greatly increased the rate of cysteinyl LT prodcution 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.