Abstract 1928 Neonatal Pulmonology II: Oxidant and Inflammatory Lung Injury Poster Symposium, Tuesday, 5/4

In order to determine if G-CSF administration accentuates lung injury caused by hyperoxia and mechanical hyperventilation, 21 newborn piglets (1-3 days of age, 0.9-1.8 kg) were studied. Five groups of piglets were studied as follows: Group 1 were controls and received room air (RA) and no mechanical ventilation (n=4); Group 2 were normally ventilated (PaCO2 = 35-45 torr) with RA for 48 hours (n=5); Group 3 received 100% oxygen and hyperventilation (PaCO2 = 15-25 torr) for 48 hours (n=5); Group 4 were also normally ventilated with RA for 48 hours and received G-CSF (10 µg/kg) IV at 0, 12, 24, and 36 hours (n=4); Group 5 were hyperventilated with 100% oxygen for 48 hours and received G-CSF (10 µg/kg) IV at 0, 12, 24, and 36 hours (n=4). Complete blood counts (CBC) and differentials were obtained at baseline and daily during the study. At the end of the study period, animals were sacrificed, the lungs removed en-bloc and bronchoalveolar lavage (BAL) was performed with buffered saline, cell counts determined after cytocentrifugation and Wright staining and lung tissue was flash frozen for further analyses. At the start of the experiments, CBC data were similar in all groups and did not change significantly in groups 2 and 3 animals over the 48 hour period. Neutrophil counts increased from 4,900 at baseline to 57,000 at 48 hours in group 4 animals and from 4,900 to 36,000 in group 5 animals (p<0.001 ANOVA). In BAL, group 1 animals had significantly lower total white blood cell counts compared to the other 4 experimental groups (p<0.05). There were no other significant changes between groups in BAL or lung tissue markers of lung inflammation and injury including neutrophil chemotaxis, total protein, albumin, and malondialdehyde assays following G-CSF exposure. Data indicate that despite increasing peripheral neutrophil counts as much as 10-12 fold following exposure to G-CSF, there was no increased evidence of acute lung injury or inflammation. It appears that the peripheral blood and alveolar space are two separate compartments. This suggests that prophylactic administration strategies using G-CSF to prevent sepsis in premature infants should not increase the risk for developing acute and chronic lung injury.

Supported by Amgen Corporation, Thousand Oaks, CA.