Effects of granulocyte colony-stimulating factor on the kinetics of inflammatory cells in the peripheral blood and pulmonary lesions during the development of bleomycin-induced lung injury in rats.
We evaluated the effects of granulocyte colony-stimulating factor (G-CSF) on the kinetics of inflammatory cells during the development of inflammation in bleomycin (BLM)-induced lung injury. G-CSF (100 microg/kg/day, s.c.) was administered to rats treated with or without BLM (2 mg/200 microl, intratracheally) for up to 14 days (Day 14) immediately after BLM treatment. In the BLM + G-CSF group, the lung injury score increased on Days 1 and 14, and the score of lung fibrosis on Day 14, respectively. Except for neutrophils, there were no effects of G-CSF on the number of inflammatory cells both in the peripheral blood and in the lung in both BLM-treated and -untreated rats at the acute inflammatory phase. In the G-CSF-treated groups, the number of neutrophil counts in the peripheral blood drastically increased on Day 1, temporally decreased on Day 3, and increased again on Days 7 and 14. The number of neutrophils in the lung markedly increased on Day 1 and then remained at a plateau level until Day 14. The neutrophil alkaline phosphatase score in the lung commenced to increase on Day 1, reached the maximal level on Day 7, and then remained at a plateau level until Day 14. Correlations between the numbers of neutrophils in the lung and the peripheral blood or the lung lesion score were only observed on Day 14. These findings suggest that the exacerbating effect of G-CSF on the lung injury coincided with the increase in the number of alkaline phosphatase-positive neutrophils infiltrating in the pulmonary lesion at the acute inflammatory phase and it lasted to the fibrogenic phase. The exacerbating effect of G-CSF on the severe BLM-induced lung injury seems to be related not only to the pulmonary accumulation of activated neutrophils but also to the severity of lung injury caused by the direct effects of BLM.
Adachi
Kenji
K
Department of Safety Assessment, Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan. adachiknj@chugai-pharm.co.jp
Suzuki
Masami
M
Sugimoto
Tetsurou
T
Uetsuka
Koji
K
Nakamaya
Hiroyuki
H
Doi
Kunio
K
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D004195:Disease Models, Animal; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D001761:Bleomycin; D016179:Granulocyte Colony-Stimulating Factor; D000469:Alkaline Phosphatase