Antenatal betamethasone changes cord blood monocyte responses to endotoxin in preterm lambs

Pediatr Res. 2004 May;55(5):764-8. doi: 10.1203/01.PDR.0000120678.72485.19. Epub 2004 Feb 18.


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 micromol at 5 h, 8.7 +/- 2.9 micromol at 24 h, and 4.1 +/- 1.9 micromol at 48 h versus 16.4 +/- 3.6 micromol in control animals; at 7 d, the hydrogen peroxide production increased to 74.3 +/- 19.7 micromol (p < 0.05, per 10(6) 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex Hormones
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis
  • Betamethasone / pharmacology*
  • Cells, Cultured
  • Endotoxins / metabolism*
  • Escherichia coli / metabolism
  • Female
  • Fetal Blood / drug effects*
  • Fetal Blood / metabolism
  • Glucocorticoids / pharmacology
  • Hydrogen Peroxide / metabolism
  • Hydrogen Peroxide / pharmacology
  • Inflammation
  • Interleukin-6 / metabolism
  • Leukocyte Count
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Neutrophils / metabolism
  • Phagocytosis
  • Sheep
  • Sodium Chloride / metabolism
  • Time Factors


  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Endotoxins
  • Glucocorticoids
  • Interleukin-6
  • Sodium Chloride
  • Betamethasone
  • Hydrogen Peroxide