Effects of Immunostimulatory CpG-Oligodeoxynucleotides of Bronchial Asthma in Rat

Lee, Sin Hyung; Kim, Je Hyeong; Jeong, Hye cheol; Kim, Kyung Kyu; Jung, Ki Hwan; Kim, Byung Gyu; Lee, Seung Heon; Park, Sang Myun; Sin, Cheol; Cho, Jae Youn; Shim, Jae Jeong; In, Kwang Ho; Yoo, Se Hwa; Kang, Kyung Ho

Abstract

BACKGROUND
AND OBJECT: Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the TH1-type immune response and down-regulate the TH2-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperrestponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma.
MATERIALS AND METHODS
10 normal controls(NC) and 26 asthmatic rats, which were generated by ovallbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl)on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-(TH1-type cytokine) and IL-4(TH2-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue.
RESULTS
In the BALF of the CpG group, the IFN-Î³ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5Ac gene expression was observed between the CpG group and the Ac group.
CONCLUSION
ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the TH1-type immune response with the down-regulation of the TH2-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.