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.
Adachi
Kenji
K
Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co, Ltd, Shizuoka, Japan. adachiknj@chugai-pharm.co.jp
Suzuki
Masami
M
Sugimoto
Tetsurou
T
Yorozu
Keigo
K
Takai
Hirotake
H
Uetsuka
Koji
K
Nakayama
Hiroyuki
H
Doi
Kunio
K
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