EFFECT OF DIFFERENT SENSITIZING HAPTENS ON INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSION AND CYTOKINE PRODUCTION BY NORMAL HUMAN KERATINOCYTES

In allergic contact dermatitis, different types of sensitizers are usu ally defined; however, it is not known whether the keratinocytes, whic h represent the first target cells in vivo, are differently activated by these chemicals. Our aim was to assess the effect of sensitizing ha ptens [nickel, the prohapten/immunogenic hapten: para-phenylenediamine (pPD degrees)/Bandrowski's base (BB) and dinitrosulfobenzene (DNSB)] in the induction of the intercellular adhesion molecule-1 (ICAM-1) and the production of cytokines by normal human keratinocytes cultured in a defined medium. Using FACS analysis, ICAM-1 expression at 24 hrs wa s found to be induced in a dose-dependent manner with all the haptens tested in non-toxic concentrations. Ni-2+, known as a weak sensitizer, is the most potent inducer of ICAM-1. In comparison with controls, th e addition of Ni2+, pPD, BB and DNSB to keratinocyte cultures induced a significant increase in the three forms of IL-1 (alpha, beta and rec eptor antagonist (RA)), IL-8 TNF-alpha production at 24 hrs and 48 hrs detectable by ELISA in the supernatants and the cell extracts of trea ted cells. Whereas similar amounts of TNF-alpha are released by the ke ratinocytes stimulated by the different haptens, pPD and BB induced th e highest production of IL-1 alpha, IL-1-RA and IL-8. Taken together, these data confirm the existence of direct interactions between the di fferent haptens studied and epidermal cells which might play a role in the local reaction during allergic contact dermatitis. However, the k eratinocyte activation state is not directly correlated with the commo nly reported sensitizing properties of the different haptens tested.