Th2-biased immune responses are important in a murine model of chronic hypersensitivity pneumonitis.
BACKGROUND
Chronic hypersensitivity pneumonitis (HP) can lead to irreversible pulmonary fibrosis. A good animal model is essential to elucidate the mechanisms of this disease. We previously reported that a Th2 predominance may play an important role in the fibrogenesis in chronic HP patients. A study was undertaken to evaluate whether Th2-biased immune responses were crucial during the processes of lung fibrosis in a murine model of chronic HP.


METHODS
Instillation of pigeon dropping extracts (PDE) was conducted 3 days a week for 6 or 12 weeks in C57BL/6, BALB/c and A/J mice to establish models of chronic HP. We evaluated the histopathological features, immunohistochemistry, collagen content, bronchoalveolar lavage fluid (BALF) profiles and Th1/Th2 cytokines in BALF or lung tissue with RT-PCR and ELISA.


RESULTS
Thickening of the alveolar walls and structural alterations were observed only in the A/J mice after 12 weeks of exposure to PDE. The fibrosis scores were significantly increased in 12-week A/J mice compared to those in the other strains. Immunohistochemistry evaluation showed that PDE was engulfed by alveolar macrophages that were incorporated into the alveolar septa of 12-week A/J mice. Interleukin (IL)-4 mRNA increased significantly in 6- and 12-week A/J mice. IL-13 mRNA showed a significant increase in 12-week A/J mice compared with 6-week A/J mice. TGF-β1 mRNA at 12 weeks was significantly increased in A/J mice compared with the other groups.


CONCLUSIONS
Th2-biased genetic backgrounds may play an important role in fibrosing processes in the present chronic HP model.
Mitaka
Keiko
K
Department of Integrated Pulmonology, Tokyo Medical and Dental University, Tokyo, Japan.
Miyazaki
Yasunari
Y
Yasui
Makito
M
Furuie
Masashi
M
Miyake
Shuji
S
Inase
Naohiko
N
Yoshizawa
Yasuyuki
Y
D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines