AN IN-VIVO IN-VITRO STUDY OF THE USE OF A HUMAN SKIN EQUIVALENT FOR IRRITANCY SCREENING OF FATTY-ACIDS

A human skin equivalent (HSE) consisting of reconstructed epidermis on a fibroblast-populated collagen gel was evaluated as a model for irri tancy screening. The irritancy potential of a series of saturated and unsaturated fatty acids was investigated in vivo under short-term expo sure conditions using transepidermal water loss (TEWL), laser Doppler velocimetry (LDV) and the penetration of hexyl nicotinate as parameter s. The effects of the fatty acids in vitro were studied after topical application on HSE using changes in epidermal morphology, changes in i nterleukin (IL)-1 alpha and interleukin-8 mRNA expression and protein levels, and alterations in activity of plasminogen activators as endpo ints. The unsaturated fatty acids increased both TEWL and LDV and elev ated IL-1 alpha and IL-8 mRNA levels, whereas their effects on protein levels were minimal. In contrast, the saturated fatty acids were not very effective in vivo but induced an increase in IL-1 alpha protein l evels. The type of fatty acid determines not only the way and the exte nt of skin barrier modulation, but also the pattern of cell mediator p roduction and release. This study stresses the neccessity of investiga ting multiple endpoints for the characterization of a test compound, i n particular when studying mild and moderate irritants. (C) 1997 Elsev ier Science Ltd.