Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics

BACKGROUND/AIMS: The androgen dehydroepiandrosterone (DHEA) attenuates allergic inflammatory airway reactions by down-regulating the Th2 response in mice. The purpose of this study was to investigate whether DHEA suppresses Th2 cytokine production in cultured peripheral blood mononuclear cells (PBMCs) from asthmatic patients. METHODS: Sixty-one consecutive suspected asthmatic or non-asthmatic men underwent tests for asthma. PBMCs from each subject were cultured with and without DHEA (0.01~10 micrometer) for 48 h. The concentrations of interferon (IFN)-gamma, interleukin (IL)-5, and IL-10 in the culture supernatant were measured via an enzyme-linked immunosorbent assay. RESULTS: In PBMCs from subjects exhibiting methacholine airway hyperresponsiveness (AHR), DHEA significantly suppressed IL-10, IL-5, and IFN-gamma production in a dose-dependent manner (all p<0.001) and tended to increase the IFN-gamma/IL-5 ratio (p=0.087). DHEA (10 micrometer) suppressed cytokine production to a greater degree in subjects with AHR compared with those without AHR (IL-5: 24.0+/-7.8% vs. 40.9+/-3.6%, p<0.01; IFN-gamma: 29.7+/-7.0% vs. 54.5+/-5.1%, p<0.01). Cytokine suppression was significantly related to AHR, serum total IgE levels, and skin reactivity to house dust mites. CONCLUSIONS: DHEA suppressed both Th1 and Th2 responses, with a Th1 bias, and the degree of suppression was associated with the severity of AHR or atopy. Therefore, DHEA may be a useful therapy for asthma.

BCG-Induced Dendritic Cell Responses and Suppression of Interleukin-5 Production from T Cells in Atopic Asthmatics

Bacille Calmette-Guerin (BCG) induces potent Th1 responses with the help of interleukin (IL)-10 and IL-12 released from dendritic cells (DCs), and suppresses Th2- associated allergic reactions. However, there are still some controversies on therapeutic effects of BCG in asthmatics. This study investigated whether BCG administration to DCs suppresses IL-5 production from T cells in atopic asthmatics. DCs derived from peripheral blood of subjects were cultured with or without BCG and Dermatophagoides farinae extract. Some DCs were co-cultured with T cells in the presence of BCG or the above culture supernatants. In the atopic asthmatics, BCG significantly increased IL-10 and IL-12 production from DCs. In the presence of D. farinae extract, BCG further increased IL-10 production. BCG-induced IL-10 production was significantly higher in the atopics (n=14) than in the non-atopics (n=9). Both BCG and the BCG-treated DCs culture supernatant significantly increased IFN-gamma production from T cells. Both BCG and the supernatant from DCs+BCG+D. farinae co-cultures significantly decreased IL-5 production (all p<0.05), but the supernatant from DCs+BCG co-cultures did not. In conclusion, administration of BCG together with D. farinae extract effectively decreased IL-5 production from T cells, probably through the action of IL-10 and IL-12 released from DCs in D. farinaesensitive asthmatics.

Inoculation route-dependent effects of BCG on asthmatic airway histology / 대한내과학회지

BACKGROUND: Intranasal (i.n.), as compared with subcutaneous (s.c.), BCG vaccination causes a greater suppression of airway eosinophilia. A comprehensive examination is needed to confirm that in various asthma models. METHODS: BALB/c mice were immunized with i.n. or s.c. inoculation of BCG 1 x 10(5) CFUs. Sensitization and provocaton using ovalbumin (OVA) or Dermatophagoides farinae (Der f) were started at the same time or 1 week after the immunization. And then, a bronchoalveolar lavage (BAL) and an examination of lung tissue using a computerized image analyzer program were performed. RESULTS: Both the i.n.- and s.c.- BCG infections reduced eosinophilia in both the BAL fluids and the lung tissues of both OVA- and Der f- asthma models. The proportions of BAL fluid lymphocyte in the mice infected with i.n. BCG were significantly lower than those with s.c. BCG (1.60+/-0.39% vs. 3.42+/-0.37%, p1,000 micrometer) airways: 17.4+/-3.2 vs 37.0+/-5.9/mm2, p<0.05]. The goblet cell proportions in epithelium were also significantly lower in the mice received s.c.- as compared with i.n.- BCG (0.29+/-0.18 vs 0.43+/-0.20, p<0.01). CONCLUSIONS: These results suggest that both i.n.- and s.c.- BCG inoculations reduce eosinophilia in airways, but the s.c. route is more effective in the suppression of the asthmatic responses in lung tissue.

Suppressive effect of dehydroepiandrosterone on the development of asthmatic reaction in BALB/c mice / 천식및알레르기

BACKGROUND: Dehydroepiandrosterone (DHEA), an adrenal androgen, may regulate Th1/Th2 cytokines. OBJECTIVE: To determine whether DHEA have a preventive effect against the development of asthma, a Th2-associated disease. MATERIALS AND METHODS: Female BALB/c mice were fed with a standard diet incorporated with 0.1% (w/w) of DHEA for 1 week before sensitization with ovalbumin (OVA, 20 microgram i.p. twice with 2-week intervals). Enhanced pause (Penh) was monitored after 1% OVA inhalations for 3 successive days, and then the methacholine bronchoprovocation tests were performed using a whole-body plethysmography system. Analyses of inflammatory cells, cytokines, and OVA-specific IgE were carried out. RESULTS: Both the excessive airway narrowing (maximum Penh) and the airway hypersensitivity (PC200, mg/mL) to methacholine were significantly suppressed with the DHEA pretreatment (P<.05 and P<.01, respectively). However, the numbers of the inflammatory cells and the levels of interleukin (IL)-4, IL-5, and interferon (IFN)-gamma in the bronchoalveolar lavage fluid, the production of IL-4, IL-5, and IFN-gamma by Con A-stimulated splenocytes, and the serum IgE level in DHEA group were not significantly different from those in asthma group. CONCLUSION: DHEA pretreatment could suppress the development of asthmatic airway hyperresponsiveness without suppression of Th2 cytokines and airway inflammation.