Shivji, G. M., D. K. Stetsko, and D. N. Sauder. Epidermal Cytokine Gene Expression: An In Vitro Assay for Irritants and Allergens. J. Invest. Dermatol. 1992. 98(4): 613 (Abstract #367). [Reprinted by permission of Blackwell Science, Inc.] 

Development and validation of in vitro methods for dermal irritation/toxicity testing is aimed at establishing simple and reliable assays that eliminate the need for animals in toxicity testing. Grading the irritation potentials of irritants and allergens using cultured human keratinocytes can be facilitated by monitoring multiple endpoints. However, it is important to identify in vitro endpoints that are predictive of in vivo toxicity. Since cytokines are involved in cutaneous inflammation we investigated the effect of allergens and irritants on the induction of cytokine mRNA in keratinocytes as a potential in vitro assay for allergens and irritants. These studies revealed that certain groups of chemicals were significant inducers of cytokine mRNA, i.e. allergens induced a 2-fold increase in M-CSF, and a 5 to 6-fold increase in GM-CSF over reactive chemicals, whereas irritants had a 2 to 3-fold increase in TNFa. Induction of IL-1, IL-6, and GM-CSF was also seen. Using the unique properties of keratinocytes to express different cytokines upon stimuli may assist in classifying chemicals into irritants and contact sensitizers. In addition, the regulation of cytokines by allergens and irritants will aid in the understanding of the pathobiology of these reactions.