Racial differences across pregnancy in maternal pro-inflammatory immune responsivity and its regulation by glucocorticoids

The distribution of adverse pregnancy, birth and subsequent child developmental and health outcomes in the U.S. is characterized by pronounced racial (particularly Black-white) disparities. In this context, chronic stress exposure represents a variable of considerable importance, and the immune/inflammatory system represents a leading candidate biological pathway of interest. Previous pregnancy studies examining racial disparities in immune processes have largely utilized circulating cytokine levels, and have yielded null or mixed results. Circulating cytokines primarily represent basal secretion and do not necessarily represent functional features of immune responsivity and regulation. Thus, in order to conduct a more in-depth characterization of racial differences in functional immune properties during pregnancy, we utilized an ex vivo stimulation assay, a dynamic measure of immune function at the cellular level, to investigate Black-white racial differences in in mid- and late-gestation in i) pro-inflammatory (IL-6) responsivity of leukocytes to antigen [lipopolysaccharide (LPS)] challenge, and ii) regulation (dampening) of this pro-inflammatory response by glucocorticoids. 177 women (N = 42 Black (24%), n = 135 white (76%)) with a singleton, intrauterine pregnancy provided 20 mL venous blood in mid- (16.6 ± 2.4 wks) and late (33.3 ± 1.1 wks) pregnancy. Maternal pro-inflammatory responsivity of leukocytes was quantified by assessing the release of the pro-inflammatory cytokine IL-6 in response to LPS stimulation, and regulation of the pro-inflammatory response was quantified by assessing the suppression of the stimulated IL-6 response after co-incubation with progressively increasing levels of dexamethasone [10-7, 10-6, 10-5 M] (i.e., glucocorticoid receptor resistance (GRR)). A priori model covariates included maternal age, parity, SES (socioeconomic status), and pre-pregnancy BMI. Maternal pro-inflammatory responsivity (LPS-stimulated IL-6) and GRR increased significantly across mid- and late gestation (adjusted β = 0.157, p = 0.007; β = 0.627, p