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Toxicologic Pathology
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Effects of Granulocyte Colony-Stimulating Factor (G-CSF) on Bleomycin-Induced Lung Injury of Varying Severity

Kenji Adachi

Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan, adachiknj{at}chugai-pharm.co.jp, Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan

Masami Suzuki

Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan

Tetsurou Sugimoto

Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan

Keigo Yorozu

Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan

Hirotake Takai

Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan

Koji Uetsuka

Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan

Hiroyuki Nakayama

Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan

Kunio Doi

Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan

We evaluated the effects of granulocyte colony-stimulating factor (G-CSF) on bleomycin (BLM)-induced lung injury that developed diffuse alveolar damage and subsequent pulmonary fibrosis (PF) of varying severity. G-CSF (100 µg/kg/day) was administered subcutaneously to BLM (0.2, 20, 2,000 µg)-treated or -untreated rats for 3 or 14 days. In the BLM 0.2 µg group, slight alveolar mononuclear cell infiltration was observed, although PF was not noted. In the BLM 20-µg and 2,000-µg groups, diffuse alveolar damage along with neutrophil infiltration and subsequent PF were observed. In the saline + G-CSF group and BLM 0.2 µg + G-CSF group, a marked increase in the number of alkaline phosphatase (ALP)-positive neutrophils was noted in the alveolar capillaries, although there was neither neutrophil infiltration in alveoli nor exacerbation of lung injury. In the BLM 20 µg + G-CSF and BLM 2,000 µg + G-CSF groups, an exacerbation of lung injury along with an increase in the number of ALP-positive neutrophils in the alveoli was observed. These results indicate that the administration of G-CSF to rats with slight lung injury bearing no PF does not exacerbate the lung injury. The exacerbating effects of G-CSF seem to be associated not only with the marked infiltration of activated neutrophils but also with the severity of underlying lung injury.

Key Words: Granulocyte colony-stimulating factor • bleomycin • lung injury • pulmonary fibrosis • neutrophil alkaline phosphatase • rat • histopathology.

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Toxicologic Pathology, Vol. 31, No. 6, 665-673 (2003)
DOI: 10.1080/01926230390244924
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