Release of markedly increased quantities of prostaglandin D-2 from the skin in vivo in humans after the application of cinnamic aldehyde

Background: Cinnamic aldehyde is a common fragrance additive in foods and v arious health and beauty products. Application of cinnamic aldehyde to the skin of humans can induce cutaneous vasodilatation characterized by erythem a, urticaria, and stinging. Previous studies have suggested that prostaglan dins (PGs) may mediate the vasodilation, but the causative PG has not been established. We have shown that cutaneous vasodilatation induced by compoun ds such as sorbic acid and methylnicotinate is mediated by PGD(2). Objective: Our purpose was to determine whether cutaneous vasodilatation in duced by cinnamic aldehyde is mediated by PGD(2) in humans. Method and Results: Topical application of 1% cinnamic aldehyde to the fore arms of 3 human volunteers resulted in cutaneous flushing and 25- to 42 fol d increases in the levels of the major circulating metabolite of PGD(2), 9 alpha, 11 beta -PGF(2), in blood drawn from the antecubital vein draining t he treated sites. There was no increase in other vasodilatory mediators, in cluding PGE(2), PGI(2), or histamine. The release of PGD(2) Nas concentrati on dependent. Cutaneous vasodilatation and PGD2 release were markedly decre ased by the administration of aspirin, but were not significantly altered b y pretreatment with the selective cyclooxygenase-2 inhibitor rofecoxib, sug gesting that thr formation of PGD, is dependent on cyclo-oxygenase-1. Conclusion: The cutaneous vasodilatation induced by cinnamic aldehyde is me diated to a large extent by the release of PGD, from a cellular source in t he skin.