Intervention by azithromycin on bleomycin-induced lung injury in rats and its mechanisms.

OBJECTIVE

To study the role of Th1/Th2 balance in the pathogenesis of pulmonary fibrosis and to investigate the therapeutic mechanisms of azithromycin.

METHODS

Male wistar rats were randomly divided into three experimental groups: the bleomycin A(5) (BLM) group (BLM group), the azithromycin (AZI) group (AZI group) and the control group. Quantitative analysis of the histopathologic changes was performed by computer gray scan. The expression of IL-10 mRNA and IFN-gamma mRNA was examined by RNase protection assay (RPA).

RESULTS

(1) In the BLM group, up-regulation of IL-10 mRNA was stronger than that of IFN-gamma mRNA, resulting in the inversion of the IL-10/IFN-gamma mRNA ratio, a shift from the Th1-like response of IFN-gamma predominance in the control group to the Th2-like response of IL-10 predominance in the BLM group. (2) The oral administration of AZI inhibited the expression of IL-10 and IFN-gamma mRNA; reversed the Th2-like response in the BLM group to the Th1-like response on day 7; and decreased the exudation of inflammatory cells as well as the degree of fibrosis.

CONCLUSIONS

(1) At the early stage of fibrosing alveolitis, Th2 domination and the lack of IFN-gamma in the presence of alveolar epithelial and basement membrane injury may promote the development of fibrosis. (2) Azithromycin can inhibit the expression of IL-10 and IFN-gamma, and reverse the Th2-like response in the BLM group to a Th1-like response, and as a result, decrease the inflammatory injury as well as the degree of BLM-induced lung injury in rats.