Increased Releasability of Skin Mast Cells after Exercise in Patients with Exercise-induced Asthma

The role of lung mast cells in exercise-induced asthma (EIA) is controversial. To investigate whether the skin mast cell releasability is increased after exercise in EIA, 49 young atopic men with or without asthma took part in a free-running test for 6 min and were given skin prick tests using morphine, a mast cell secretagogue, before and after the exercise. The mean diameters of the wheal induced by morphine in patients with EIA were not significantly different from those in patients without EIA before exercise, although the baseline lung function was significantly lower and the airway hyperresponsiveness, the peripheral blood eosinophil count, and the size of the wheal in response to Dermatophagoides pteronyssinus were significantly higher in patients with EIA. However, the differences of the morphine-induced wheal diameter between patients with EIA and those without EIA became significant at 120 min after exercise (p<0.05), while the responses to histamine were not significantly different. These results suggest that exercise increases the releasability of skin mast cells in EIA patients whose asthma/allergy are relatively severe

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

Bacille Calmette-Guérin (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-γ 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. farinae-sensitive asthmatics

Effects of Cytokine Milieu Secreted by BCG-treated Dendritic Cells on Allergen-Specific Th Immune Response

Bacillus Calmette-Guérin (BCG) is reported to suppress Th2 response and asthmatic reaction. Dendritic cells (DCs), the major antigen-presenting cells, infections with BCG are known to result in inducing various cytokines. Thus, DCs are likely to play a role in the effects of BCG on asthma. This study aims at investigating that cytokine milieu secreted by BCG-treated DCs directly enhances allergen-specific Th1 response and/or suppresses Th2 response in allergic asthma. DCs and CD3+ T cells were generated from Dermatophagoides farinae-sensitive asthmatics. DCs were cultured with and without BCG and subjected to flow cytometric analysis. IL-12 and IL-10 were determined from the culture supernatants. Some DCs were cocultured with T cells in the presence of D. farinae extracts after adding the culture supernatants from BCG-treated DCs, and IL-5 and IFN-γ were determined. BCG-treated DCs enhanced significantly the expressions of CD80, CD86, and CD40, and the productions of IL-12 and IL-10. Addition of culture supernatants from BCG-treated DCs up-regulated production of IFN-γ by T cells stimulated by DCs and D. farinae extracts (p<0.05), but did not down-regulate production of IL-5 (p>0.05). The cytokine milieu secreted by BCG-treated DCs directly enhanced allergen-specific Th1 response, although did not suppress Th2 response