Corsini, E. Selective Induction of Keratinocyte Cytokines by Chemical Allergens. ATLA 1999. 27: 114.

Irritant and allergic contact dermatitis are two very similar diseases, and differentiating between them clinically can be difficult. In the screening of topically applied drugs, cosmetics and other chemicals for human use, it should be very important, both from a safety and an economic point of view, to have biological markers to discriminate these events which have different impacts on human health. Recently, cytokines have been identified as useful tools for differentiating between irritant and allergic contact dermatitis. A study by Enk & Katz PNAS, USA 89, 1398-1402, 1992) addressed the early events that occur following allergen treatment of the skin of non-sensitised mice to identify cytokine production that may be critical in the induction of allergic contact dermatitis. These investigators demonstrated, by using semi-quantitative RT-PCR analysis, that only contact allergens, such as TNCB, DNFB, or DNCB up-regulated keratinocyte derived IL-1a, IP-10 and MIP-2. More recently, IL-12, a cytokine important for the development of a Th1 response, has been shown to be selectively induced in vivo in keratinocytes by contact allergens, while vehicles or irritants failed to induce its production (Muller et al. Journal of Clinical Investigation 94, 1799-1805, 1996). Due to their anatomical location, keratinocytes are among the first cells to be exposed to various antigens which yield Th1 immune responses, and the use of these cells in a simplified in vitro model to evaluate the potential toxicity of chemicals destined for epicutaneous application is amply justified. The in vivo studies clearly proved that keratinocyte-derived cytokines, such as IL-1a or IL-12, might serve as differentiating markers of allergic and irritant reactions. Recent experimental evidence produced by our group indicates that the selective up-regulation of cytokines by chemical allergens can also be reproduced in vitro. In particular, using a murine keratinocyte cell line, we demonstrated that only contact sensitisers are able to increase in a dose-dependent fashion the level of cell-associated IL-1a. Furthermore, using a reconstituted human epidermis, a selective induction of IL-12 by chemical allergens has been demonstrated, confirming the in vivo findings.