title: IL-1beta stimulates alveolar fluid absorption in fetal guinea pig lungs via the hypothalamus-pituitary-adrenal gland axis.
abstract: We tested the hypothesis that interleukin (IL)-1beta-induced cortisol synthesis stimulates alveolar fluid clearance in preterm fetuses. IL-1beta was administered subcutaneously daily to timed-pregnant guinea pigs for 3 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 in 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-1beta, which both were attenuated by cortisol synthesis inhibition. Plasma ACTH and cortisol concentrations were increased by IL-1beta at both gestational ages, and metyrapone reduced cortisol concentrations. IL-1beta was mostly low or undetectable in both fetal and maternal blood. Prenatal alveolar fluid clearance, when present as well as IL-1beta induced, was always propranolol and amiloride sensitive, suggesting that beta-adrenoceptor stimulation and amiloride-sensitive Na+ channels were critical for fluid absorption. IL-1beta increased lung beta-adrenoceptor density at gestation day 61, and cortisol synthesis inhibition attenuated the increased beta-adrenoceptor density. Epithelial Na+ channel and Na+-K+-ATPase subunit expressions were both increased by IL-1beta 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.
authors.affiliation: Dept. of Physiology and Pharmacology, Northeastern Ohio Universities, College of Medicine, 4209 State Route 44, PO Box 95, Rootstown, OH 44272-0095, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Ye
authors.forename: Reshma
authors.initials: R
authors.lastname: Acharya
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Herbert
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hamilton
authors.forename: Hans G
authors.initials: HG
authors.lastname: Folkesson
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D004837:Epinephrine / Q000097:blood; D053503:Epithelial Sodium Channels; D015633:Extravascular Lung Water / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007375:Interleukin-1 / Q000097:blood / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D053503:Epithelial Sodium Channels; D007375:Interleukin-1; D015222:Sodium Channels; D000324:Adrenocorticotropic Hormone; D000254:Sodium-Potassium-Exchanging ATPase; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine