Skin metabolism of contact allergens

Skin possesses metabolic capacity which may be significant for chemicals with direct skin effects. The conversion of some chemical contact allergens from an inactive to an active hapten has also been described. Eugenol and isoeugenol are contact allergens that fit this description, but despite close chemical similarity, they are not cross-reactive and this has led to the hypothesis that they may be activated by different mechanisms. There is evidence that eugenol follows a phenolic radical mechanism, while isoeugenol undergoes demethylation followed by oxidation to the orthoquinone. Since these reactions may be cytochrome P-450 mediated (the former being cytochrome P4501A driven) we investigated how modulation of this system affects skin sensitization to eugenol and isoeugenol. Using the local lymph node assay, which measures lymphocyte proliferation in draining lymph nodes, the effect of clotrimazole, an inhibitor of epidermal cytochrome P4501A, was assessed. Clotrimazole enhanced the response to eugenol and potassium dichromate (an irrelevant contact allergen) approximately two-fold and isoeugenol five-fold. It was anticipated that clotrimazole would have little effect on isoeugenol sensitization, but that through inhibition of cytochrome P4501A, eugenol sensitization would be reduced. However, the present data suggest that the presence of P4501A in skin may result in the metabolism of these chemicals to relatively harmless moieties.