title: Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice.
abstract: 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-beta(1) 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-beta(1) 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.
authors: Division of Pulmonary Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Fumitake
authors: F
authors: Saito
authors: Sadatomo
authors: S
authors: Tasaka
authors: Ken-Ichiro
authors: K
authors: Inoue
authors: Keisuke
authors: K
authors: Miyamoto
authors: Yasushi
authors: Y
authors: Nakano
authors: Yuko
authors: Y
authors: Ogawa
authors: Wakako
authors: W
authors: Yamada
authors: Yoshiki
authors: Y
authors: Shiraishi
authors: Naoki
authors: N
authors: Hasegawa
authors: Seitaro
authors: S
authors: Fujishima
authors: Hirohisa
authors: H
authors: Takano
authors: Akitoshi
authors: A
authors: Ishizaka
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D002908:Chronic Disease; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D000903:Antibiotics, Antineoplastic; D015850:Interleukin-6; D001761:Bleomycin