An integrated model for the differentiation of chemical-induced allergic and irritant skin reactions

Contact and photocontact allergic as well as irritant and photoirritant ski n reactions represent a major problem in clinical dermatology and during th e development of new pharmaceuticals. Furthermore, there is a lack of in vi tro and in vivo assays that provide a clear differentiation between allergi c and irritant skin reactions. Here, we describe an integrated model to dif ferentiate between chemical-induced allergic and irritant skin reactions by measuring objective and easy-to-determine parameters within both skin and skin-draining lymph nodes. Dose-response studies with standard contact and photocontact allergens as well as irritants and photoirritants revealed tha t irritants predominantly induced skin inflammation, which in turn stimulat ed draining lymph node cell proliferation. In contrast, the induction phase of contact or photocontact allergy was characterized by marginal skin infl ammation, but a marked activation and proliferation of skin-draining lymph node cells. Therefore, a differentiation index (DI) was defined describing the relation between skin-draining lymph node cell activation (lymph node c ell count index) and skin inflammation (ear swelling). A DI > 1 indicates a n allergic reaction pattern whereas DI < 1 demonstrates an irritant potenti al of a chemical. Experiments with the contact allergen oxazolone, the phot ocontact allergen TCSA + UVA, the irritant croton oil, and the photoirritan t 8-methoxypsoralen + UVA confirmed the predictive value of DI. Furthermore , flow cytometric analysis of lymph node-derived T- and B-cell subpopulatio ns revealed that contact sensitizer, but not irritant, induced the expressi on of CD69 on the surface of I-A(+) cells. In conclusion, further studies w ith a broad range of irritants and allergens will be required to confirm ge neral applicability. (C) 1998 Academic Press.