Abstract
Corticosteroids are routinely administered to women at risk for preterm delivery to induce fetal lung maturation. Antenatal corticosteroids have immunomodulatory effects on fetal immune cells that are poorly understood. We hypothesized that maternal betamethasone would alter in fetal monocytes both the initiation of inflammation in response to pro-inflammatory stimuli and the resolution of inflammation by phagocytosis of apoptotic neutrophils. Preterm lambs at 124 d gestation were delivered 15 h, 1 d, 2 d, or 7 d after 0.5 mg/kg maternal intramuscular betamethasone. Monocytes from cord blood were isolated and cultured and results were compared with monocytes from preterm lambs exposed to maternal saline or monocytes from adult sheep. Phagocytosis of Escherichia coli was not changed, however, phagocytosis of apoptotic neutrophils was low in fetal monocytes but increased after 7 d exposure to maternal betamethasone to the level found in adult monocytes. Hydrogen peroxide production after endotoxin stimulus was significantly reduced to 7.1 ± 2.2 μ mol at 5 h, 8.7 ± 2.9 μ mol at 24 h, and 4.1 ± 1.9 μ mol at 48 h versus 16.4 ± 3.6 μ mol in control animals; at 7 d, the hydrogen peroxide production increased to 74.3 ± 19.7 μ mol (p < 0.05, per 106 monocytes). IL-6 production was reduced at 15 h after maternal betamethasone but at no other time point. Maternal betamethasone initially suppressed several fetal monocyte functions, however, at 7 d, measurements of initiation and resolution of inflammation were increased to levels similar to monocytes from adult sheep. The time-dependent changes in maternal betamethasone modulation of the responses of fetal monocytes may influence immune function of the preterm lamb after delivery.
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Abbreviations
- BPD:
-
bronchopulmonary dysplasia
- GA:
-
gestational age
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Supported by grants HL-65397 and HD-12714 from the National Institutes of Health.
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Kramer, B., Ikegami, M., Moss, T. et al. Antenatal Betamethasone Changes Cord Blood Monocyte Responses to Endotoxin in Preterm Lambs. Pediatr Res 55, 764–768 (2004). https://doi.org/10.1203/01.PDR.0000120678.72485.19
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DOI: https://doi.org/10.1203/01.PDR.0000120678.72485.19
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