The effect of BCG treatment on the remodelling in the House Dust Mite-induced allergic asthma in mice

Kwon, Soon Seog; Kim, Chi Hong; Ahn, Joong Hyun; Kim, Seung Joon; Lee, Sook Young; Kim, Young Kyoon; Kim, Kwan Hyoung; Moon, Hwa Sik; Song, Jeong Sup; Park, Sung Hak; Kim, Young Sill

Abstract

BACKGROUND: Airway remodelling has been linked to the development of airway hyperresponsiveness. However, current treatments have little control the airway remodelling in asthmatic patients. Recently BCG immunization induce immunomodulation that was attributed to the ability of helper T cell type 1 (TH1) immune response. In order to investigate the effect of BCG on the remodelling in the Houst Dust Mite (HDM) induced allergic asthma in mice, we observed the change of airway remodelling, allergic inflammatory responses and airway hyperresponsiveness in the asthmatic mice on going allergic responses after BCG via subcutaneous injection.
METHODS
4-6-week-old female BALB/c mice were divided into three groups; mice in BCG group received 2 X 10(4) colony-forming units/100 micro L of BCG subcutaneously on days 14, 21 and 28, whereas mice in asthma group received phosphate buffer saline (PBS). Subsequently, mice in asthma and BCG groups were immunization and intranasal challenge with HDM for 9 weeks. On days 60, 61 and 62, two groups received an intranasal dose of 10 micro gram HDM and then enhanced pause was monitored. The mice were examined for the extent of the goblet cell hyperplasia, the thickness of subepithelial fibrosis and peribronchial smooth muscle. Analyses of immunoglobuline E (IgE) response, HDM- specific IgG1 and IgG2a responses in serum, cytokine pattern and eosinophilia in bronchoalveolar lavage (BAL) were carried out.
RESULTS
Control group did not show goblet cell hyperplasia, but asthma group showed a significant increase in the extent of goblet cell hyperplasia. There was a significant increase in the thickness of subepithelial fibrosis and peribronchial smooth muscle in the asthma group in comparing with the control group (p<0.01). Comparison of BCG and asthma groups showed statistically significant differences in goblet cell numbers, thickness of peribronchial smooth muscle (p<0.01). BCG group were most significantly protected from airway hyperresponsiveness to methacholine, BAL eosinophilia (p<0.01), BAL fluid IL-4 levels (p<0.01), serum total IgE (p<0.01) and HDM-specific IgG1 (p<0.01). No changes were observed IL-10, IL-13, interferon-gamma and Transforming growth factor-beta levels in the BAL fluid and the thickness of subepithelial fibrosis.
CONCLUSION
These data suggest that BCG could be effective in the treatment of the chronic changes of airways due to asthma and associated with the induction of TH1 immune response.