ABSTRACT
Background: Female neonates are well-recognised to have
improved outcomes compared to males. The mechanisms remain poorly
understood, but hormonal influences on immune function may contribute to
the female advantage during infection and inflammation. The aim of this
study was to investigate the in vitro treatment effects of
17β-estradiol (E2) and its antagonism in males versus females on CD14+
monocyte cell surface receptor (TLR4, CD11b, ER-α, ER-β) expression and
reactive oxygen species (ROS) production from mononuclear cells in
umbilical cord blood (UCB) and adult blood.
Methods: UCB samples were collected from term neonates and
whole blood was collected from adults (M:F n=10 in each group).
Mononuclear cells were isolated via density gradient centrifugation and
flow cytometry was used to assess receptor expression and ROS production
in the presence of E2, ICI 182,780 (ER antagonist), or
lipopolysaccharide (LPS/endotoxin) in various combinations.
Results: Basal expression of TLR4, CD11b, ER-α and ER-β did not
differ on monocytes between sexes or between adults versus neonates.
Treatment with E2, ICI 182,780, or LPS individually or in combination
did not modulate CD11b or TLR4 expression in neonates or adults. Higher
expression of monocyte ER-β expression was noted in female versus male
adults following ICI 182,780 treatment alone (p<0.05). Female
neonates exhibited less ROS production following LPS and E2 treatment in
combination compared to male neonates (p<0.05).
Conclusion: The influence of E2 on neonatal mononuclear cell
ROS production provides preliminary evidence for sex-specific
disparities in neonatal immune function. These responses may be amenable
to immunomodulation.
Key words: 17-β-Estradiol; Monocyte; Reactive Oxygen Species;
Immunomodulation; Neonates.