No abstract

These data suggest that ozone can induce alveolar epithelial cell proliferation in a dose-dependent manner, and that alveolar epithelial cell proliferation is correlated with airway obstruction.

Both BCG and dehydroepiandrosterone (DHEA) induce Th1 immune responses and suppress Th2 allergic reactions. To investigate whether the combination of BCG and DHEA has an additive effect on asthma prevention, BALB/c mice (n = 10 per group) were given an intraperitoneal injection of BCG at the beginning of sensitization, and fed mice chow containing DHEA throughout the study. In female mice, the combined administration of 2 x 10(4) CFUs BCG and 0.01% DHEA effectively suppressed the ovalbumin-induced increase in airway sensitivity to methacholine (56.5 vs. 8.2 mg/mL, p < 0.01), while BCG (13.9 mg/mL) or DHEA (17.9 mg/mL) alone did not. However, the addition of high dose (0.1%) DHEA decreased the efficacy of high dose (2 x 10(5) CFUs) BCG in suppressing the airway responsiveness and eosinophilia. In male mice, the treatments with BCG and/or DHEA were less effective, and the interferon-gamma/interleukin-4 ratio in the splenocyte supernatant was significantly higher and the ovalbumin-specific IgE concentration in the serum was significantly lower as compared to female mice. In conclusion, the combination of low doses of BCG and DHEA had an additive effect in suppressing the development of airway hypersensitivity. Androgens in males and DHEA overdose might reduce the efficacy of BCG.

Intranasal bacille Calmette-Guérin (BCG) vaccination causes greater suppression of ovalbumin-induced airway eosinophilia in mice than does subcutaneous vaccination. Coadministration of ovalbumin with interleukin (IL)-18 induces an ovalbumin-specific Th1 immune reaction. The purpose of this study was to examine whether the suppressive effect of BCG is dependent on the inoculation method, using various murine asthma models. Female BALB/c mice (n = 7 per group) were immunized with BCG subcutaneously or intranasally, then sensitized with ovalbumin or Dermatophagoides farinae either immediately or one week later. After provocation with one of the allergens, the mice were tested by methacholine bronchial challenge, and analyses of the inflammatory cell numbers in the airways and cytokine levels in the supernatant of concanavalin A-stimulated splenocytes were conducted. Overall, the airway responses to the allergens were significantly lower and the interferon (IFN)-gamma level was significantly higher in BCG-treated mice than in untreated mice, and the number of airway eosinophils was significantly related to the IFN-gamma/IL-5 ratio (r = -0.444, p < 0.001). Subcutaneous BCG inoculation tended to have a greater suppressive effect on the development of airway hyperresponsiveness and eosinophilia than did intranasal inoculation. Concurrent BCG vaccination and D. farinae sensitization one week before ovalbumin sensitization tended to have a greater suppressive effect on airway responsiveness to methacholine induced by D. farinae aerosols than did that induced by ovalbumin aerosols. Subcutaneous BCG inoculation suppressed asthmatic reactions more remarkably than did intranasal inoculation, and concurrent BCG vaccination and allergen sensitization induced allergen-specific suppression of asthmatic reactions.

SummaryNatural killer T (NK T) cells have been shown to play an essential role in the development of allergen-induced airway hyperresponsiveness (AHR) and/or airway inflammation in mouse models of acute asthma. Recently, NK T cells have been reported to be required for the development of AHR in a virus induced chronic asthma model. We investigated whether NK T cells were required for the development of allergen-induced AHR, airway inflammation and airway remodelling in a mouse model of chronic asthma. CD1d-/-mice that lack NK T cells were used for the experiments. In the chronic model, AHR, eosinophilic inflammation, remodelling characteristics including mucus metaplasia, subepithelial fibrosis and increased mass of the airway smooth muscle, T helper type 2 (Th2) immune response and immunoglobulin (Ig)E production were equally increased in both CD1d-/-mice and wildtype mice. However, in the acute model, AHR, eosinophilic inflammation, Th2 immune response and IgE production were significantly decreased in the CD1d -/-mice compared to wild-type. CD1d-dependent NK T cells may not be required for the development of allergen-induced AHR, eosinophilic airway inflammation and airway remodelling in chronic asthma model, although they play a role in the development of AHR and eosinophilic inflammation in acute asthma model.