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.