Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women

Abstract

Pregnancy is a period of considerable physiological adaption in neuroendocrine, cardiovascular, as well as immune function. Understanding of typical changes in inflammatory immune responses during healthy pregnancy is incomplete. In addition, despite considerable racial difference in adverse pregnancy outcomes, data are lacking on potential racial differences in such adaptation. This repeated measures prospective cohort study included 37 Black and 39 White women who provided blood samples during early, mid-, and late pregnancy and 8–10 weeks postpartum. Peripheral blood mononuclear cells were incubated with lipopolysaccharide (LPS) for 24 hours and supernatants assayed by electrochemiluminescence to quantify interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1β, and IL-8 production. While no changes were observed in IL-8 production over time, significant increases in IL-6, TNF-α, and IL-1β production were observed from early to late pregnancy, with subsequent declines approaching early pregnancy values at postpartum (ps<.05). Overall, inflammatory response patterns were highly similar among Black versus White women. However, Black women had greater TNF-α production during mid-pregnancy (p=.002) and marginally lower IL-1β production at postpartum (p=.054). These data show a clear trajectory of change in the inflammatory immune response across pregnancy and postpartum. In this cohort of generally healthy women, Black and White women exhibited minimal differences in LPS-stimulated cytokine production across the perinatal period. Future prospective studies in Black and White women with healthy versus adverse outcomes (e.g., preeclampsia, preterm birth) would inform our understanding of the potential role of immune dysregulation in pregnant women and in relation to racial disparities in perinatal health.

Fetal sex is associated with maternal stimulated cytokine production, but not serum cytokine levels, in human pregnancy

“…In relation to LPS-stimulated cytokine production, we have previously reported longitudinal changes across time in this study sample (Gillespie et al, 2016). Our prior report showed IL-6 and TNF-α production increased from early to mid-pregnancy, as well as mid- to late pregnancy.…”

“…In addition, an increase from early to mid-pregnancy was observed in IL-1β production. No significant changes were found in IL-8 production across pregnancy (Gillespie et al, 2016). …”

“…Pregnant women exhibit heightened serum levels of certain proinflammatory cytokines as well as greater lipopolysaccharide (LPS) stimulated proinflammatory cytokine production than non-pregnant adults (e.g., Brewster et al, 2008; Vassiliadis et al, 1998). Although limited, longitudinal examinations have demonstrated significant increases in some serum and LPS-stimulated cytokines across pregnancy, including serum TNF-α, stimulated IL-6, and stimulated IL-1β, while other markers exhibit a decline, such as serum IL-8 (Christian and Porter, 2014; Gillespie et al, 2016). Information regarding factors which may modify such adaptation is limited.…”

Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

“…VEGF is also known as a somewhat weak agonist for vasodilator production (through its ability to weakly mobilize Ca 2+ ), and this may be beneficial for late-pregnancy support of uterine blood flow. Later in pregnancy, the role of inflammatory hormones are less well defined, though circulating concentrations change throughout gestation (Gillespie et al 2016). Of note, abnormally high levels may even be detrimental.…”

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing

“…African American women, specifically, appear to be most susceptible to early birth via the inflammatory pathway (Frey et al, 2016; Menon et al, 2009). Indeed, inflammatory responses are tightly regulated during pregnancy (Christian & Porter, 2014; Gillespie, Porter, & Christian, 2016) and, like the alternative instigating pathways, inflammation ultimately promotes the classical signs and symptoms of labor: cervical dilation, uterine contraction, and rupture of fetal membranes (Romero, Dey, & Fisher, 2014; Shynlova, Lee, Srikhajon, & Lye, 2013). …”