Fetal Treatment with Interleukin-1α Improves Postnatal Lung Function in Premature Lambs. ♦ 1494

Background: Interleukin-1 (IL-1) denotes two proinflammatory cytokines, IL-1α and IL-1β. Levels of IL-1 are increased in intra-amniotic infections and in other inflammatory conditions. IL-1 may affect the defence functions of the lung. Intraamniotic IL-1α was shown to up regulate the expression of surfactant proteins A and B in preterm rabbits (K. Bry, et al AJ Resp Crit Care Med, Vol. 151, A23). Objective: We measured the physiological and biochemical lung responses in preterm lambs to intra-amniotic injection of IL-1α. Methods: Ewes carrying singleton 126±1 day gestational age fetuses were randomize to receive 125 μg IL-1α (n=8) or placebo (n=9) via ultrasound guided intra-amniotic injection. Each lamb was delivered 48 h after treatment by cesarian section and mechanically ventilated for 2 h. Results: Over the 2 h ventilation period the dynamic compliance of IL-1α treated lambs was higher than controls (0.36±0.02 vs 0.28±.02 (mean ± S.E.) ml/kg/cm H₂O, P<0.05). Lung volumes measured from post mortem pressure volume curves trended higher for IL-1atreated lambs than for controls (36±6 vs 24±5 ml/kg at 40 cm H₂O pressure and 28±6 vs 18±4 ml/kg at 10 cm H₂O). Saturated phosphatidylcholine in the lung, a measure of surfactant pool size, was higher for IL-1α treated animals than for controls (77±7 vs 54±3 μmol/kg, P<0.005). As a measure of pulmonary edema, total lung recovery of I¹²⁵ albumin injected at 1.5 h of life tended to be less in IL-1α treated animals than in controls(5.2±0.8 vs 7.3±1.2%). Plasma cortisol at 2 h of age was higher in IL-1α treated lambs than in controls (3.4±0.7 vs 1.5±0.2, P<0.02), although cord blood cortisol and catecholamine levels were similar between the groups. Comparisons of IL-1α treated animals versus controls showed no differences in total white blood cells, differential percentages, or absolute neutrophils. Cardiac output and regional blood flow also were similar between the groups. Conclusion: Fetal treatment with IL-1α increased surfactant pool size, improved dynamic compliance, and was not associated with an inflammatory response, in utero cortisol response, or differences in other indicators of fetal or newborn well being.