Di-(2-ethylhexyl)
phthalate (
DEHP) has been widely used in
polyvinyl chloride products and has become ubiquitous in the developed countries.
DEHP reportedly displays an adjuvant effect on
immunoglobulin production. However, it has not been elucidated whether
DEHP is associated with the aggravation of
atopic dermatitis. We investigated the effects of
DEHP on
atopic dermatitis-like skin lesions induced by mite
allergen in NC/Nga mice. NC/Nga male mice were injected intradermally with mite
allergen on their right ears. In the presence of
allergen,
DEHP (0, 0.8, 4, 20, or 100 microg) was administered by
intraperitoneal injection. We evaluated clinical scores, ear thickening, histologic findings, and the
protein expression of
chemokines. Exposure to
DEHP at a dose of 0.8-20 microg caused deterioration of
atopic dermatitis-like skin lesions related to mite
allergen; this was evident from macroscopic and microscopic examinations. Furthermore, these changes were consistent with the
protein expression of proinflammatory molecules such as macrophage inflammatory protein-1alpha (MIP-1alpha) and eotaxin in the ear tissue in overall trend. In contrast, 100 microg
DEHP did not show the enhancing effects. These results indicate that
DEHP enhances
atopic dermatitis-like skin lesions at hundred-fold lower levels than the no observed adverse effect level determined on histologic changes in the liver of rodents.
DEHP could be at least partly responsible for the recent increase in
atopic dermatitis.