SENSITIZATION TO 2,4-DINITROCHLOROBENZENE - INFLUENCE OF VEHICLE ON ABSORPTION AND LYMPH-NODE ACTIVATION

Effective skin sensitization is dependent upon immune activation of ly mph nodes draining the site of exposure. The influence of vehicle form ulation on the vigour of lymph node cell proliferative responses to 2, 4-dinitrochlorobenzene (DNCB) has been examined. Mice (BALB/c strain) were exposed topically to 0.5% DNCB dissolved in either acetone or pro pylene glycol (PG). A significantly greater lymph node cell proliferat ive response was induced by DNCB in acetone. The observed differences were not attributable to variations in the numbers of immunostimulator y dendritic cells accumulating in the draining nodes following sensiti zation. In parallel studies, the absorption and cutaneous disposition of DNCB dissolved in acetone or PG were measured in vitro using static diffusion cells and full thickness mouse skin. Although flux of DNCB through the skin was comparable with both vehicles over 24 h, the abso rption of the allergen during the first 4 h of exposure was significan tly faster when acetone was used as the vehicle. Localization of DNCB demonstrated that much less of the chemical allergen was present in th e skin at 4 h when applied in PG vehicle. However, there were no measu rable vehicle effects on skin disposition of DNCB at 24 h. These data indicate that the sensitization potential of DNCB is influenced signif icantly by the nature of the vehicle used, possibly due to consequenti al effects on chemical absorption and disposition. The studies describ ed in this paper reveal that the application vehicle may have a signif icant influence on the ability of DNCB to induce immune activation of draining lymph nodes and hence skin sensitization and that this may in turn be associated with important changes in the absorption and/or di sposition of the chemical within the skin.