Effects of Th2 pulmonary inflammation in mice with bleomycin-induced pulmonary fibrosis.
OBJECTIVE
Leucocytes, especially lymphocytes and neutrophils, as well as alveolar macrophages, that infiltrate into the lung are involved in the development of pulmonary fibrosis. However, the role of T helper (Th)2-type inflammation, mediated by Th2 cells and eosinophils, in fibrosis remains unknown. Transgenic mice deficient in the transcriptional repressor, Bcl6, display an attenuation of Th2 cytokine production. We studied the effects of Th2-type pulmonary inflammation on bleomycin-induced pulmonary fibrosis using Bcl6 transgenic mice.


METHODS
Bleomycin was administered to ovalbumin (OVA)-sensitized Bcl6 transgenic and wild-type mice by intratracheal instillation during sequential OVA antigen challenge. Concentrations of transforming growth factor-beta1 in the BAL fluid were measured 2 weeks after bleomycin administration. At the same time lung tissue was examined histopathologically, and homogenized to assess collagen levels and Th1/Th2 cytokine mRNA expression.


RESULTS
Although OVA-sensitized, bleomycin-treated Bcl6 transgenic mice had markedly lower numbers of eosinophils in both BAL and lung tissue compared with OVA-sensitized, bleomycin-treated wild-type mice, the development of pulmonary fibrosis in response to bleomycin was similar in Bcl6 transgenic mice and wild-type mice.


CONCLUSIONS
These results suggest that Th2-dominant inflammation in the lung is not essential for the development of bleomycin-induced pulmonary fibrosis.
Hirata
Hirokuni
H
Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Tochigi, Japan. hirokuni@dokkyomed.ac.jp
Arima
Masafumi
M
Fukushima
Yasutsugu
Y
Ishii
Yoshiki
Y
Tokuhisa
Takeshi
T
Fukuda
Takeshi
T
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000503:physiopathology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1
D051560:Proto-Oncogene Proteins c-bcl-6; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D010047:Ovalbumin; D004247:DNA