Products of arachidonic acid metabolism and the effects of cyclooxygenase inhibition on ongoing cutaneous allergic reactions in human beings.
BACKGROUND
There have been conflicting reports about the effects of inhibition of arachidonic acid metabolism on early- and late-phase cutaneous reactions. We re-examined this question with a unique nonsteroidal antiinflammatory drug, tenidap sodium. Tenidap sodium has been demonstrated in in vitro studies to inhibit cyclooxygenase, lipoxygenase, and cytokine production (interleukin-1, interleukin-6, tumor necrosis factor-alpha).


METHODS
In a double-blind, randomized, crossover study, seven pollen-sensitive subjects ingested tenidap (120 mg, by mouth, daily) and placebo for 9 days with a 3-week washout period between treatments. On the eighth day they underwent allergen skin testing, measurable for up to 12 hours, and on the ninth day they underwent 5-hour skin chamber exposures to allergen and buffer. Chamber fluids were analyzed for cellular content, neutrophil granule protein release, cyclooxygenase and lipoxygenase arachidonic acid metabolites, histamine, and tryptase.


RESULTS
Tenidap did significantly inhibit cyclooxygenase metabolites at both antigen and buffer sites but had no effect on histamine, tryptase, lipoxygenase metabolites, or granulocyte infiltration. Neutrophil granule release of lactoferrin was lower at the antigen site during tenidap administration, but there was no reduction of elastase release. Prostaglandin E2 and leukotriene E4 increased significantly at antigen sites compared with buffer sites during placebo administration and were the most prominent arachidonic acid metabolites detected.


CONCLUSIONS
Tenidap, despite inhibiting cyclooxygenase release at antigen sites, had no effect on skin test responses to antigen or on antigen-induced mediator release or granulocyte infiltration. We conclude that cyclooxygenase metabolites are not important in the development of an allergic cutaneous inflammatory response.
Atkins
P C
PC
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6057.
Zweiman
B
B
Littman
B
B
Presti
C
C
von Allmen
C
C
Moskovitz
A
A
Eskra
J D
JD
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D004311:Double-Blind Method; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D000078183:Oxindoles; D012882:Skin Tests
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D000078183:Oxindoles; D016718:Arachidonic Acid; C062866:tenidap