SELECTIVE INDUCTION OF TYPE-2 CYTOKINES FOLLOWING TOPICAL EXPOSURE OFMICE TO PLATINUM SALTS

Repeated topical exposure of BALB/c strain mice to organic chemical re spiratory allergens, such as trimellitic anhydride (TMA), or contact a llergens such as 2,4-dinitrochlorobenzene (DNCB), provokes characteris tic cytokine secretion profiles consistent with the divergent activati on of discrete T cell subpopulations. Under such conditions, lymph nod e cells (LNC) isolated from animals exposed to TMA elaborated comparat ively large amounts of the type 2 cytokines interleukin 10 (IL-IO) and mitogen-inducible interleukin 4 (IL-4), but only low levels of the ty pe 1 product interferon gamma (IFN-gamma). In contrast, DNCB-activated LNC displayed the converse (type 1) cytokine secretion profile; We ha ve now examined cytokine production induced by topical application to mice of respiratory sensitizing platinum salts; ammonium tetrachloropl atinite II, ammonium hexachloroplatinate IV and cis-dichlorodiammine p latinum II. Metal salts were dissolved in dimethyl sulfoxide (DMSO). C ytokine secretion profiles were compared with those elicited following concurrent exposure to TMA or DNCB or to the vehicle acetone:olive oi l (AOO) alone. All three platinum salts and TMA stimulated vigorous IL -4 and IL-10 production compared with DNCB-activated LNC; vehicle-stim ulated LNC failed to elaborate detectable levels of either cytokine. H owever, DNCB and the DMSO vehicle provoked substantial IFN-gamma expre ssion, whereas exposure to AOO vehicle resulted in a considerably weak er IFN-gamma response. Levels of this cytokine induced by treatment wi th respiratory allergens were, in the majority of cases, substantially lower than those observed with the relevant vehicle. Indeed, an inver se dose-response relationship far IFN-gamma expression was exhibited b y all three platinum salts, suggestive of the elaboration by platinum salt activated LNC of an inhibitory factor or factors for IFN-gamma. T hese data suggest that it may be possible to identify those metal salt s with respiratory sensitizing potential as a function of induced type 2 cytokine secretion patterns. (C) 1998 Elsevier Science Ltd. All rig hts reserved.