Chronic and repeated Chlamydophila pneumoniae lung infection can result in increasing IL-4 gene expression and thickness of airway subepithelial basement membrane in mice.

ABSTRACT

BACKGROUND/PURPOSE: Chlamydophila pneumoniae infection has been associated with several pulmonary and cardiac diseases. However, it has not been explored for its ability to activate the same immunopathologic mechanisms of asthma, namely, a predominant Th2 immune response and structural changes that are termed airway remodeling. This study evaluated immune responses in the lung and airway pathology of BALB/c mice with chronic and repeated C. pneumoniae infections. METHODS: Mice were inoculated intranasally with 5 x 10(6) inclusion-forming units of C. pneumoniae TWAR strain, and re-inoculated at 14 and 42 days after the primary inoculation. Cytokine gene expression in bronchoalveolar lavage (BAL) cells was analyzed by RT-PCR on day 70. Airway pathology was also evaluated by morphometric measurements. RESULTS: A significant increase of interleukin (IL)-4 mRNA was detected in BAL cells in infected mice, and a significant increase in subepithelial basement membrane thickness of the airways was also noted in infected mice as compared with control mice (8.95 +/- 0.28 microm vs. 5.54 +/- 0.22 microm, p < 0.0001). We further analyzed the correlation between IL-4 cytokine expression and the increased subepithelial basement membrane thickness of airways in infected mice. We found that mice with increased IL-4 mRNA expression had significant increases in the thickness of subepithelial basement membrane as compared with mice without increased IL-4 mRNA expression (9.87 +/- 0.51 microm vs. 6.49 +/- 0.52 microm, p < 0.0001). CONCLUSION: It is believed that our results demonstrated for the first time that chronic and repeated infections with C. pneumoniae increased IL-4 gene expression and thickness of airway subepithelial basement membrane in mice.