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 i nhibition of arachidonic acid metabolism on early- and late-phase cuta neous reactions. We re-examined this question with a unique nonsteroid al antiinflammatory drug, tenidap sodium. Tenidap sodium has been demo nstrated 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 tre atments. On the eighth day they underwent allergen skin testing, measu rable for up to 12 hours, and on the ninth day they underwent 5-hour s kin chamber exposures to allergen and buffer. Chamber fluids were anal yzed for cellular content, neutrophil granule protein release, cycloox ygenase and lipoxygenase arachidonic acid metabolites, histamine, and tryptase. Results: Tenidap did significantly inhibit cyclooxygenase me tabolites at both antigen and buffer sites but had no effect on histam ine, tryptase, lipoxygenase metabolites, or granulocyte infiltration. Neutrophil granule release of lactoferrin was lower at the antigen sit e during tenidap administration, but there was no reduction of elastas e release. Prostaglandin E(2) and leukotriene E(4) increased significa ntly at antigen sites compared with buffer sites during placebo admini stration and were the most prominent arachidonic acid metabolites dete cted. Conclusion: Tenidap, despite inhibiting cyclooxygenase release a t antigen sites, had no effect on skin test responses to antigen or on antigen-induced mediator release or granulocyte infiltration. We conc lude that cyclooxygenase metabolites are not important in the developm ent of an allergic cutaneous inflammatory response.