Effects of granulocyte colony-stimulating factor on hyperoxia-induced lung injury in newborn piglets.
Granulocyte colony-stimulating factor (G-CSF) increases the concentration and activation of neutrophils in the peripheral blood and has been used to prevent late-onset infection in premature infants. However, if G-CSF also augmented the inflammatory response in the lung, the incidence and severity of acute and chronic lung injury might be expected to increase. Using a newborn piglet model of acute lung injury, we examined the effects of rhG-CSF (recombinant-metHuG-CSF) on lung injury. Thirty-three newborn piglets were studied as follows: 1). Unventilated controls; 2). normally ventilated (PaCO2 = 35-45 torr) with room air(RA) for 48 h; 3). normally ventilated with RA for 48 h and received rhG-CSF (10 mg/kg/dose IV) at 0, 12, 24, and 36 h; 4). hyperventilated (PaCO2 = 15-25 torr) with 100% O2 for 48 h; 5) hyperventilated with 100% O2 for 48 h and received rhG-CSF (10 mg/kg/dose IV) at 0, 12, 24 and 36 h. Complete blood counts and and differentials were performed at 0, 24, and 48 h. Animals were sacrificed at 48 h, lungs were removed en bloc, and bronchoalveolar lavage (BAL) was performed. Total blood white blood cells and neutrophil counts increased significantly over 48 h in animals who received rhG-CSF either with normoventilation (p <0.0001) or hyperventilation with 100% O2 (p <0.003), and did not change significantly in the other experimental groups. However, there were no significant differences in BAL total cell counts, neutrophil chemotaxis activity, total protein, or albumin concentrations among the groups. Despite significantly increasing peripheral neutrophil counts, rhG-CSF did not potentiate acute lung injury or inflammation. This suggests that prophylactic administration strategies using rhG-CSF to prevent sepsis in premature infants should not increase the risk for developing acute and chronic lung disease.
Wolkoff
L I
LI
Department of Pediatrics (Neonatology), Winthrop-University Hospital, SUNY Stony Brook School of Medicine, 259 First Street, Mineola NY 11501, USA.
Levine
C R
CR
Koo
H C
HC
LaGamma
E F
EF
Pollack
S
S
Chester
D
D
Bashore
J
J
Davis
J M
JM
D000388:Air; D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018496:Hyperoxia / Q000150:complications* / Q000188:drug therapy*; D007958:Leukocyte Count; D008168:Lung / Q000098:blood supply*; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology*; D055370:Lung Injury; D009504:Neutrophils / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D013552:Swine
D016179:Granulocyte Colony-Stimulating Factor; D010100:Oxygen