A noninflammatory interleukin-1beta fragment stimulates fetal lung fluid absorption in guinea pigs.
نویسندگان
چکیده
We have previously demonstrated that full-length interleukin (IL)-1beta can induce and stimulate lung fluid absorption in near-term guinea pig fetuses via stimulation of fetal cortisol synthesis and release. To develop a potentially clinically useful drug, we tested the hypothesis that maternal administration of a noninflammatory IL-1beta-fragment (IL-1beta(Fr)) induced cortisol synthesis and stimulated lung fluid absorption in preterm fetuses. IL-1beta(Fr) was administered s.c. 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 into the lungs, and lung fluid absorption was measured over 1 h by mass balance. Lung fluid absorption was induced at 61 days and stimulated at 68 days gestation by IL-1beta(Fr), which both were attenuated by cortisol synthesis inhibition. Moreover, induction of labor by oxytocin stimulated lung fluid absorption at 61 days but had no stimulatory effect at 68 days gestation when given with the IL-1beta(Fr). Plasma adrenocorticotropin and cortisol concentrations were increased by IL-1beta(Fr) at 61 days gestation and remained high but unstimulated by IL-1beta(Fr) at 68 days gestation, and metyrapone always reduced cortisol concentrations. Prenatal lung fluid absorption, when present as well as IL-1beta(Fr)-induced, was always propranolol- and amiloride-sensitive, suggesting that beta-adrenoceptor stimulation and the epithelial Na(+) channel (ENaC) were critical for the induced/stimulated lung fluid absorption. ENaC expression was increased by IL-1beta(Fr) and attenuated by cortisol synthesis inhibition. Thus, our results suggest a potential clinical use of IL-1beta(Fr) therapeutically to induce lung fluid absorption in fetuses at risk of preterm delivery.
منابع مشابه
Stimulation of MAP kinase pathways after maternal IL-1β exposure induces fetal lung fluid absorption in guinea pigs
BACKGROUND We tested the hypothesis that maternal interleukin-1beta (IL-1beta) pretreatment and induction of fetal cortisol synthesis activates MAP kinases and thereby affects lung fluid absorption in preterm guinea pigs. METHODS IL-1beta was administered subcutaneously daily to timed-pregnant guinea pigs for three days. Fetuses were obtained by abdominal hysterotomy and instilled with isosmo...
متن کاملIL-1beta stimulates alveolar fluid absorption in fetal guinea pig lungs via the hypothalamus-pituitary-adrenal gland axis.
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 isos...
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We tested the hypothesis that oxytocin-induced labor augmented IL-1beta-induced/-stimulated lung fluid absorption in preterm guinea pig fetuses. IL-1beta was administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. At day 3, oxytocin was administered, and fetuses were delivered by abdominal hysterotomy ...
متن کاملA Noninflammatory Interleukin-1 Fragment Stimulates Fetal Lung Fluid Absorption in Guinea Pigs
We have previously demonstrated that full-length interleukin (IL)-1 can induce and stimulate lung fluid absorption in nearterm guinea pig fetuses via stimulation of fetal cortisol synthesis and release. To develop a potentially clinically useful drug, we tested the hypothesis that maternal administration of a noninflammatory IL-1 -fragment (IL-1 Fr) induced cortisol synthesis and stimulated lun...
متن کاملIL-1 stimulates alveolar fluid absorption in fetal guinea pig lungs via the hypothalamus-pituitary-adrenal gland axis
Ye, Xin, Reshma Acharya, Jonathan B. Herbert, Sarah E. Hamilton, and Hans G. Folkesson. IL-1 stimulates alveolar fluid absorption in fetal guinea pig lungs via the hypothalamus-pituitaryadrenal gland axis. Am J Physiol Lung Cell Mol Physiol 286: L756–L766, 2004. First published November 26, 2003; 10.1152/ ajplung.00214.2003.—We tested the hypothesis that interleukin (IL)1 -induced cortisol synt...
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عنوان ژورنال:
- The Journal of pharmacology and experimental therapeutics
دوره 320 2 شماره
صفحات -
تاریخ انتشار 2007