Attenuation of house dust mite Dermatophagoides farinae-induced airway allergic responses in mice by dehydroepiandrosterone is correlated with down-regulation of TH2 response.

Abstract

Dehydroepiandrosterone (DHEA), an abundant androgen in circulation, has important immunomodulating effects on T-cell differentiation; however, it is not known whether this hormone influences allergic responses. We have established a murine model of airway inflammation induced by house dust mite Dermatophagoides farinae (Der f). Der f challenge of sensitized mice would elicit a pulmonary eosinophilic inflammation. In the present study, we employed this model system to explore the effect of DHEA on allergic responses. Female BALB/c mice were fed with a standard diet incorporated with 1.5% (w/w) of DHEA for 1 week before sensitization and every other day for an additional 2 weeks after sensitization. After intratracheal inoculation of allergen, the Der f-induced airway inflammation, immunoglobulin (Ig)E antibody production, and cytokine expression were compared between control and DHEA-fed mice. In control mice the Der f-induced eosinophilia in bronchoalveolar lavage (BAL) fluids was accompanied by an increase in production of interleukin (IL)-4, IL-5, and interferon IFN-gamma systemically and locally. DHEA supplementation did not affect the body weight of mice. However, in mice that were receiving DHEA, the numbers of eosinophils and lymphocytes in BAL fluids significantly decreased at days 2 and 6 after challenge as compared with control mice. Concomitantly, total IgE antibody concentrations as well as IL-4, IL-5, and IFN-gamma levels in BAL fluids or serum also significantly reduced. Immunocytochemical staining of BAL cells revealed that there were fewer IL-4-, IL-5-, IL-10-, but not IFN-gamma-positive stained cells in DHEA-fed mice than in mice who consumed unsupplemented diet. Reverse transcription-polymerase chain reaction analysis demonstrated DHEA decreased the expression of IL-5 and IL-10 transcripts in BAL cells. Our results showed that administration of DHEA during allergic sensitization could attenuate the subsequent allergic responses elicited by challenge, and that the suppressive effect of DHEA was associated with a down-regulation of TH2 response.