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stimulates alveolar fluid absorption in fetal guinea pig lungs via the hypothalamus-pituitary-adrenal gland axis
1 Department of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, USA
* To whom correspondence should be addressed. E-mail: hgfolkes{at}neoucom.edu.
We tested the hypothesis that IL-1
-induced cortisol synthesis stimulates alveolar fluid clearance in preterm fetuses. IL-1 was administered subcutaneously daily to timedpregnant guinea pigs for three days with and without simultaneous cortisol synthesis inhibition by metyrapone. Fetuses were obtained by abdominal hysterotomy at 61 and 68 days gestation and instilled with isosmolar 5% albumin into the lungs and alveolar fluid movement was measured over 1 h from the change in alveolar protein concentration. Alveolar fluid clearance was induced at 61 days gestation and stimulated at 68 days gestation
by IL-1, which both were attenuated by cortisol synthesis inhibition. Plasma ACTH and cortisol concentrations were increased by IL-1 at both gestation ages and metyrapone reduced cortisol concentrations. IL-1 was mostly low or undetectable in both fetal and maternal blood. Prenatal alveolar fluid clearance, when present as well as IL-1-induced, was
always propranolol- and amiloride-sensitive, suggesting that -adrenoceptor-stimulation and amiloride-sensitive Na+ channels were critical for fluid absorption. IL-1 increased lung -adrenoceptor density at gestation day 61 and cortisol synthesis inhibition attenuated the increased -adrenoceptor density. Epithelial sodium channel (ENaC) and Na+,K+-ATPase subunit expressions were both increased by IL-1 and attenuated by cortisol synthesis inhibition. These results may explain why babies delivered preterm after intrauterine
inflammation have a reduced risk of developing severe respiratory distress.
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