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

Background Dehydroepiandrosterone (DHEA), an abundant androgen in circulati on, has important immunomodulating effects on T-cell differentiation howeve r. it is not known whether this hormone influences allergic responses. Objective We have established a murine model of airway inflammation induced by house dust mite Dermatophagoides farinae (Der f). DET f challenge of se nsitized mice would elicit a pulmonary eosinophilic inflammation. in the pr esent study, we employed this model system to explore the effect of DHEA on allergic responses. Methods 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 an tibody production and cytokine expression were compared between control and DHEA-fed mice. Results In control mice the Der f-induced eosinophilia in bronchoalveolar l avage (BAL) fluids was accompanied by an increase in production of interleu kin (IL)-4, IL-5, and interferon IFN-gamma systemically and locally. DHEA s upplementation did not affect the body weight of mice. However, in mice tha t were receiving DHEA. the numbers of eosinophils and lymphocytes in BAL fl uids significantly decreased at days 2 and 6 after challenge as compared wi th control mice. Concomitantly, total IgE antibody concentrations as well a s IL-4, IL-5, and IFN-gamma levels in BAL fluids or serum also significantl y reduced. Immunocytochemical staining of BAL cells revealed that there wer e fewer IL-4-, IL-5-, IL-10-, but not IFN-gamma-positive stained cells in D HEA-fed mice than in mice who consumed unsupplemented diet. Reverse transcr iption-polymerase chain reaction analysis demonstrated DHEA decreased the e xpression of IL-5 and IL-10 transcripts in BAL cells. Conclusions 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 d own-regulation of TH2 response.