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Cysteinyl leukotrienes as mediators of staphylococcal enterotoxin B in the monkey
Author(s) -
SCHEUBER P. H.,
DENZLINGER C.,
WILKER D.,
BECK G.,
KEPPLER D.,
HAMMER D. K.
Publication year - 1987
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1987.tb01142.x
Subject(s) - enterotoxin , in vivo , metabolite , chemistry , endogeny , pharmacology , antagonist , prostanoid , receptor , medicine , biology , biochemistry , microbiology and biotechnology , escherichia coli , gene
. The role of cysteinyl leukotrienes (LTs) in the action of staphylococcal enterotoxin B (SEB) was investigated in unsensitized monkeys using inhibitors of prostanoid synthesis and LT action and by measuring generation of LT in vivo. LY 171883, a selective LTD 4 /LTE 4 receptor antagonist, proved highly efficient in inhibiting immediate‐type hypersensitivity reactions in the skin and protecting against the emetic response provoked by SEB in a concentration‐dependent manner. Inhibition of prostanoid formation by pretreatment of monkeys with indomethacin or aspirin did not influence SEB responses. Based on chromatographic and radioimmunologic analysis, the generation of endogenous cysteinyl LTs was demonstrated in vivo. The concentration of LTE 4 , the major biliary cysteinyl LT detected, increased ten‐fold and a novel cysteinyl LT metabolite in urine indicated strongly enhanced LT generation upon challenge with SEB. Cysteinyl LTs are important mediators in the patho‐physiology of SEB‐induced enteric intoxication. Therefore, cysteinyl LT antagonists may be of therapeutic value in the treatment of this intestinal disorder.