Di-(2-ethylhexyl) phthalate enhances skin sensitization to isocyanate haptens in mice

Toxicological and epidemiological studies have suggested the involvement of di-(2-ethylhexyl) phthalate (DEHP) in increases in allergies. The effects of DEHP have been implicated in the deflection to T helper 2 (Th2)-biased immune responses. However, we could not observe an adjuvant effect of DEHP in a Th2-dominant fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) mouse model when applied epicutaneously together with a hapten. In the present study, we focused whether there is a hapten to which DEHP exhibits an adjuvant effect through the epicutaneous route. BALB/c mice were epicutaneously sensitized with 2-methoxy-4-nitrophenyl isocyanate (MNICN) or phenethyl isocyanate (PEICN) in the presence or absence of phthalate esters of various kinds including DEHP. After challenge with a respective hapten, the ear-swelling response was measured to determine the level of hapten sensitization. Sensitization to MNICN and PEICN was enhanced when DEHP was present in the vehicle for the hapten preparation. The enhancement of sensitization to MNICN was accompanied by an elevated production of interferon-gamma and reduced production of interleukin-4 (IL-4), suggesting polarization to a T helper 1 (Th1)-dominant response. The results suggested that the combination of a hapten and a phthalate ester significantly affects the outcome of CHS.