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To understand better the cellular and molecular mechanisms of chemical-induced occupational asthma, we examined the effects of the Th2 cytokine antagonists interferon-gamma (IFN-gamma), interleukin (IL)-12 and anti-IL-4 on the balance of the Th1/Th2 response induced by trimellitic anhydride (TMA) and phthalic anhydride (PA). Eight- to ten-week-old BALB/c mice were assigned to be exposed to either TMA or PA plus one of these Th2 cytokine antagonists. Both TMA (25% and 12.5% for sensitization and challenge, respectively) and PA (12.5% and 6.25% for sensitization and challenge, respectively) induced a Th2 response marked by an increasing production of IL-4 and IL-10 in the supernatants of ex vivo spleen cells cultured with concanavalin A and also of serum total IgE. Co-administration of IL-12 and antiIL-4 deviated these PA- or TMA-induced Th2 responses, as judged by an increasing serum total IgG2a production (up to 14-fold), associated with a slight decrease of IL-4 in three out of four experiments and of IL-10 in all four experiments. Co-administration of IFN-gamma, however, had only one weak effect. These findings suggest that the chemical-induced Th2-biased response may be diverted during an induction period by exogenous administration of the Th2 cytokine antagonists, particularly IL-12 and the anti-IL-4 antibody. These results would significantly enhance our understanding of the Th1/Th2 response induced by chemicals.

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