Endocrine Factors Determining Immune Polarization during Perinatal Transition

Abstract

In utero the skewness of the adaptive immune system towards Th2 ('antiinflammatory') direction and low of Th1/Th2 cell ratio defend the fetus against rejection by the maternal immune system. Th2 dominance at birth is also of importance as it prevents uncontrolled inflammatory processes during parturition. This condition should change rapidly after birth. In an extrauterine milieu that is inherent with exposure to microorganisms, Th1 ('proinflammatory') polarization (i. e. increased Th1 cytokine production along with high Th1/Th2 ratio) are required to maintain an efficient immune response. After birth, maternal hormone supplies including estrogen, progesterone, testosterone, and antiinflammatory prostaglandins cease abruptly. As these hormones have an immune modulatory action favoring Th2, and inhibiting Th1 polarization, their low level supports the strengthening of Th1-type immunity. During parturition a dramatic but transient increase of several hormones (oxytocin, thyorid hormones, and catecholamines) occurs. Again, the net effect of high hormone levels favors Th2 activation, followed by Th1 polarization when hormonal levels reach their postnatal levels. The perinatal change of these components results in the quick cessation of Th1 inhibition and supports the maturation of adaptive immunity to provide an effective response against extrauterine microorganisms.

Cyclic AMP in human preterm infant blood is associated with increased TLR-mediated production of acute-phase and anti-inflammatory cytokines in vitro

“…This is in line with emerging evidence that immune function is significantly influenced by sex, but little is known about relevance of sex-specific regulation of neonatal immunity ( 26 , 27 ). Several sex hormones impact key immune cell functions and the expression of X-linked immune genes contribute to sex-specific immune responses ( 26 , 28 ). While the mechanisms underlying sex differences in neonatal immunity are largely unknown, our observation of lower cAMP concentrations in male cord blood is consistent with distinct inflammatory responses that could contribute to poorer short- and long-term outcomes in male newborns ( 29 – 31 ).…”