LORATADINE DOWN-REGULATES ICAM-1 EXPRESSION ON HUMAN KERATINOCYTES AND LANGERHANS CELLS

Intercellular adhesion molecule-1 (ICAM1) plays a crucial role in medi ating cell-cell interactions in inflammatory reactions and particularl y in allergic skin diseases. The aim of this study was to assess the e ffects of loratadine on ICAM-1-induced expression on human normal epid ermal cells, keratinocytes and Langerhans cells. ICAM-1 expression was induced on keratinocytes cultured in serum-free, low calcium medium, treated with 10 UI/ml of gamma IFN for 24 h, in the absence or presenc e of 0.25 mu M, 2.5 mu M, 25 mu M of loratadine. The induction of ICAM -1 on highly Langerhans cell-enriched suspensions was analyzed after a 24 h incubation at 37 degrees C, without gamma IFN, in the absence or presence of loratadine, as for the keratinocytes. No cytotoxic effect of loratadine was observed. Using fluorescence-activated cell sorter analysis, it could be shown that loratadine (25 mu M) significantly re duced by 20%, the number of ICAM 1 positive keratinocytes. The same co ncentration, as well as 2.5 mu M of loratadine applied to Langerhans c ells, resulted in a significant decrease of 36% and 16% respectively o f their ICAM-1 level. These results demonstrate that loratadine is abl e, in an in vitro system, to downregulate the expression of ICAM-1 on activated epidermal cells in the absence of histamine. It is suggested that loratadine may be a useful agent in antigen-specific allergic in flammatory skin reactions in which T cell/keratinocyte, T cell/Langerh ans cell binding may play an important role in the initiation and/or t he maintenance of an allergic reaction.