GRANULOCYTE MACROPHAGE-COLONY STIMULATING FACTOR (GM-CSF): POSSIBLE REGULATOR OF SURFACTANT TURNOVER DURING PERINATAL PERIOD. † 1948

Genetic absence of GM-CSF results in alveolar proteinosis, and a very slow surfactant turnover. At term the alveolar pool size of surfactant is one order of magnitude higher and the pulmonary turnover rate one order of magnitude longer than in the adult. The concentrations of GM-CSF in the amniotic fluid and lung effluent at premature birth are considerably lower than after birth(Pediatr Res 37: 198A, 1995). To test the hypothesis that GM-CSF affects surfactant turnover during the perinatal period in the rabbit, GM-CSF (5μg) was administered intra-amniotically to each fetus in one uterine horn of four does while the fetuses in the contralateral horn received placebo(PL). Fourty hrs later (day 29 of pregnancy), the animals were delivered by hysterotomy. At the age of 1 hr the animals received a trace of surfactant containing ³H-dipalmitoyl phosphatidylcholine (DPPC) and¹⁴ C-acetate intratracheally. After surfactant administration, the percent recovery of ³H-saturated PC in the cell-free bronchoalveolar lavage (BAL) and in the total lung were as follows:Table The recovery of DPPC in the lung tended to decrease faster, and the recovery of ³H-labeled lipid in the liver tended to increase more among the GM-CSF-treated than among the placebo-treated animals. The phospholipids in BAL from the GM-CSF-treated animals tended to become labeled faster with ¹⁴C than those from the controls, suggesting a more rapid de novo synthesis, transport, or secretion. We propose that exogenous GM-CSF increases the catabolism of surfactant in the newborn. It remains to be studied whether GM-CSF is a physiological regulator of surfactant turnover during perinatal period. Recombinant human GM-CSF was a generous gift of Immunex.

Table 1