Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice

Fumitake Saito, Sadatomo Tasaka, Ken Ichiro Inoue, Keisuke Miyamoto, Yasushi Nakano, Yuko Ogawa, Wakako Yamada, Yoshiki Shiraishi, Naoki Hasegawa, Seitaro Fujishima, Hirohisa Takano, Akitoshi Ishizaka

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172 Citations (Scopus)


Interleukin-6 (IL-6) is known to be involved in the pathogenesis of various inflammatory diseases, but its role in bleomycin (BLM)-induced lung injury and subsequent fibrotic changes remains to be determined. We evaluated the role of IL-6 in the lung inflammatory changes induced by BLM using wild-type (WT) and IL-6-deficient (IL-6-/-) mice. The mice were treated intratracheally with 1 mg/kg BLM and killed 2, 7, or 21 days later. Lung Inflammation in the acute phase (Days 2 and 7) was assessed by differential cell counts in bronchoalveolar lavage (BAL) fluid and cytokine levels in the lung. Lung fibrotic changes were evaluated on Day 21 by histopathology and collagen assay. On Day 2, BLM administration induced significant increases in the numbers of total cells, macrophages, and neutrophils in BAL fluid, which were attenuated in IL-6-/- mice (P < 0.05). Lung pathology also showed inflammatory cell accumulation, which was attenuated in the IL-6-/- mice compared with WT mice. In WT mice, elevated levels of TGF-b1 and CCL3 were observed 2 and 7 days after BLM challenge, respectively. On Day 7, BLM-induced inflammatory cell accumulation did not differ between the genotypes. Lung pathology 21 days after BLM challenge revealed significant fibrotic changes with increased collagen content, which was attenuated in IL-6-/- mice. Although the TGF-β1 level in the lung did not differ between the genotypes on Day 21, CCL3 was significantly lower in IL-6-/- mice. These results indicate that IL-6 may play an important role in the pathogenesis of BLM-induced lung injury and subsequent fibrotic changes.

Original languageEnglish
Pages (from-to)566-571
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Issue number5
Publication statusPublished - 2008 May 1


  • Bleomycin
  • CCL3
  • Fibrosis
  • IL-6
  • TGF-β

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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