Effects of granulocyte colony-stimulating factor (G-CSF) on bleomycin-induced lung injury of varying severity.
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 microg/kg/day) was administered subcutaneously to BLM (0.2, 20, 2,000 microg)-treated or -untreated rats for 3 or 14 days. In the BLM 0.2 microg group, slight alveolar mononuclear cell infiltration was observed, although PF was not noted. In the BLM 20-microg and 2,000-microg groups, diffuse alveolar damage along with neutrophil infiltration and subsequent PF were observed. In the saline + G-CSF group and BLM 0.2 microg + 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 microg + G-CSF and BLM 2,000 microg + 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.
Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co, Ltd, Shizuoka, Japan. adachiknj@chugai-pharm.co.jp
Kenji
K
Adachi
Masami
M
Suzuki
Tetsurou
T
Sugimoto
Keigo
K
Yorozu
Hirotake
H
Takai
Koji
K
Uetsuka
Hiroyuki
H
Nakayama
Kunio
K
Doi
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007442:Intubation, Intratracheal; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001761:Bleomycin; D016179:Granulocyte Colony-Stimulating Factor; D000469:Alkaline Phosphatase