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

• Published in: Toxicologic pathology 2003-11, Vol.31 (6), p.665-673
• Main Authors: Adachi, Kenji, Suzuki, Masami, Sugimoto, Tetsurou, Yorozu, Keigo, Takai, Hirotake, Uetsuka, Koji, Nakayama, Hiroyuki, Doi, Kunio
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - metabolism; Animals; Biological and medical sciences; Bleomycin - administration & dosage; Bleomycin - toxicity; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug toxicity and drugs side effects treatment; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - therapeutic use; Injections, Subcutaneous; Intubation, Intratracheal; Male; Medical sciences; Neutrophil Infiltration - drug effects; Neutrophils - drug effects; Neutrophils - enzymology; Neutrophils - pathology; Pharmacology. Drug treatments; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - pathology; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - pathology; Rats; Rats, Sprague-Dawley; Toxicity: respiratory system, ent, stomatology
• ISSN: 0192-6233; 1533-1601
• DOI: 10.1080/01926230390244924

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.