Granulocyte colony-stimulating factor exacerbates the acute lung injury and pulmonary fibrosis induced by intratracheal administration of bleomycin in rats.
We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on lung injury induced by intratracheal administration of bleomycin (BLM, 2 mg/200 micro1) in rats. In experiment 1, G-CSF (10, 30 and 100 microg/kg/day, s.c.) was administered to rats treated with BLM or saline for 7 days starting immediately after BLM administration. In rats receiving G-CSF alone, a large number of neutrophils were noted in the pulmonary capillaries, although there were no lung lesions. In rats receiving BLM alone, diffuse alveolar damage was observed. The administration of G-CSF to BLM-treated rats increased the total lung lesion per unit of pulmonary parenchyma (total lung lesion %) along with increases in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion in a dose-dependent fashion. In experiment 2, 100 microg/kg/day of G-CSF was administered to rats treated with BLM or saline for up to 28 days starting immediately after BLM administration. The administration of 100 microg/kg/day of G-CSF to BLM-treated rats showed no effects at 14 days but it increased the lung lesion % and the score of lung fibrosis along with the increase in the number of neutrophils infiltrating in the pulmonary lesion at 28 days. These findings suggest that G-CSF administration to BLM-treated rats influenced and exacerbated the BLM-induced acute lung injury, and also exacerbated pulmonary fibrosis in a dose-dependent fashion. The exacerbation of lung injury coincided with the marked increase in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion.
Adach
Kenji
K
Toxicology Laboratory, Chugai Pharmaceutical Co, Ltd, Shizuoka, Japan. adachikn@mail.ecc.u-tokyo.ac.jp
Suzuki
Masami
M
Sugimoto
Tetsurou
T
Suzuki
Shigeo
S
Niki
Rikio
R
Oyama
Atsushi
A
Uetsuka
Koji
K
Nakamaya
Hiroyuki
H
Doi
Kunio
K
D000208:Acute Disease; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D001761:Bleomycin / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007442:Intubation, Intratracheal; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000401:mortality / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D015996:Survival Rate
D000903:Antibiotics, Antineoplastic; D011994:Recombinant Proteins; D001761:Bleomycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor