Effects of cyclooxygenase and lipoxygenase inhibitors on inflammation associated with oxazolone-induced delayed hypersensitivity.
Oxazolone-induced delayed hypersensitivity in mice produced swelling with concomitant increased tissue levels of leukotrienes and prostaglandins. Pharmacological agents were coapplied topically with oxazolone at the time of challenge in an attempt to modulate the immune-based inflammation. Dexamethasone inhibited both swelling and increases in eicosanoid levels. Indomethacin reduced prostaglandin levels but failed to inhibit swelling or reduce leukotriene levels. L-651,896 (2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol), a 5-lipoxygenase inhibitor, reduced leukotriene levels but did not reduce swelling or prostaglandin levels. A combination of indomethacin and L-651,896 reduced eicosanoid levels but did not reduce swelling. These data suggested that the reduction in tissue levels of 5-lipoxygenase or cyclooxygenase oxygenation products of arachidonic acid either singularly or together did not result in the concomitant reduction of the inflammation associated with oxazolone-induced delayed hypersensitivity.
Meurer
R
R
Department of Biochemistry and Molecular Biology, Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
Opas
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EE
Humes
J L
JL
D000818:Animals; D016861:Cyclooxygenase Inhibitors; D003907:Dexamethasone / Q000032:analysis; D015232:Dinoprostone; D005260:Female; D006968:Hypersensitivity, Delayed / Q000378:metabolism*; D007249:Inflammation / Q000517:prevention & control*; D007975:Leukotriene B4 / Q000032:analysis; D016859:Lipoxygenase Inhibitors; D051379:Mice; D010080:Oxazoles / Q000494:pharmacology*; D010081:Oxazolone / Q000494:pharmacology*; D011458:Prostaglandins E / Q000032:analysis; D013189:SRS-A / Q000032:analysis
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010080:Oxazoles; D011458:Prostaglandins E; D013189:SRS-A; D010081:Oxazolone; D007975:Leukotriene B4; D003907:Dexamethasone; D015232:Dinoprostone