Mouse Model of Hydroquinone Hypersensitivity via Innate and Acquired Immunity and its Promotion by Combined Reagents.

We established a mouse model of contact hypersensitivity (CHS) to hydroquinone (HQ), a widespread chemical in our environment. HQ was painted onto flanks; then, HQ was challenged by painting onto ear pinnas on days 7 and 14. The CHS after the second challenge was markedly greater than that after the first challenge. Both challenges increased thymic stromal lymphopoietin and T helper type 2 cytokines in ear pinnas, whereas IFN-γ (typical T helper type 1 cytokine) was decreased, despite an increase in IL-18 (typical IFN-γ inducer). In nude mice (T cell-reduced), although a first challenge induced CHS, a second challenge did not augment it. In severe combined immunodeficient, severe combined immunodeficient-beige, and IL-1-deficient mice, CHS was not induced. However, CHS was inducible in severe combined immunodeficient-beige mice after transfer of natural killer cells from HQ-sensitized normal mice. Tretinoin (used for enhancing the skin-whitening effect of HQ) and resin monomers (used to prevent polymerization of HQ) lowered the HQ concentration needed to establish sensitization to HQ. The augmented CHS after a second challenge was reduced by JNJ7777120, dexamethasone, suplatast tosilate (T helper type 2-cytokine inhibitor), and anti-thymic stromal lymphopoietin antibody. These results suggest that (i) thymic stromal lymphopoietin, IL-1, and T and/or natural killer cells are important in establishing and augmenting CHS to HQ and (ii) inflammatory chemicals may promote CHS to HQ as adjuvants.