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Effects of granulocyte colony-stimulating factor on hyperoxia-induced lung injury in newborn piglets
L I Wolkoff1, C R Levine, H C Koo
1Department of Pediatrics (Neonatology), Winthrop-University Hospital, SUNY Stony Brook School of Medicine, 259 First Street, Mineola NY 11501, USA.
Insights
Granulocyte colony-stimulating factor (G-CSF) increases neutrophils but does not worsen lung injury in piglets. This suggests G-CSF is safe for preventing infections in premature infants, without increasing lung disease risk.
Area of Science:
- Neonatal research
- Pulmonary medicine
- Hematology
Background:
- Granulocyte colony-stimulating factor (G-CSF) boosts neutrophil levels and is used to prevent infections in premature infants.
- Concerns exist that G-CSF might exacerbate lung inflammation, potentially increasing acute and chronic lung injury.
- A newborn piglet model was utilized to investigate G-CSF's impact on acute lung injury.
Purpose of the Study:
- To determine if recombinant-metHuG-CSF (rhG-CSF) exacerbates acute lung injury in a newborn piglet model.
- To assess the effects of rhG-CSF on inflammatory markers and lung injury parameters under different ventilation conditions.
Main Methods:
- Thirty-three newborn piglets were divided into control, normoventilation, normoventilation with rhG-CSF, hyperventilation with oxygen, and hyperventilation with oxygen plus rhG-CSF groups.
- Animals were monitored for 48 hours, with blood counts taken at intervals.
- Lung injury was assessed via bronchoalveolar lavage (BAL) for cell counts, protein, and albumin levels.
Main Results:
- rhG-CSF significantly increased peripheral white blood cell and neutrophil counts in both normoventilation and hyperventilation groups.
- No significant differences were observed in BAL total cell counts, neutrophil chemotaxis, protein, or albumin concentrations across groups.
- rhG-CSF did not potentiate acute lung injury or inflammation despite increasing neutrophil counts.
Conclusions:
- Prophylactic administration of rhG-CSF in premature infants is unlikely to increase the risk of developing acute and chronic lung disease.
- G-CSF's ability to increase neutrophils does not appear to translate to heightened lung inflammation or injury in this model.
- Findings support the continued use of rhG-CSF for infection prevention in high-risk neonates.
Abstract:
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.