Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA.
Am J Reprod Immunol. 2020 Jul;84(1):e13252. doi: 10.1111/aji.13252. Epub 2020 May 23.
Disruption in homeostatic feedback loops between inflammatory mediators and the hypothalamic-pituitary-adrenal (HPA) axis is a key mechanism linking chronic stress to inflammation and adverse health outcomes, including those occurring during pregnancy. In particular, alterations in glucocorticoid sensitivity may occur as a result of chronic stress, including that due to racial discrimination, and may be implicated in the persistent adverse maternal and infant health outcomes experienced by African Americans. While there are a few large-scale studies in human pregnancy that measure both cytokines and HPA axis hormones, to our knowledge, none directly measure glucocorticoid sensitivity at the cellular level, especially in an African American population.
We measured the full range of the dexamethasone (DEX) dose-response suppression of TNF-α in first-trimester blood samples from 408 African American women and estimated leukocyte cell type contribution to the production of TNF-α.
The mean (SD) DEX level needed to inhibit TNF-α production by 50% (ie, DEX IC ) was 9.8 (5.8) nmol/L. Monocytes appeared to be the main driver of Uninhibited TNF-α production, but monocyte counts explained only 14% of the variation. Monocyte counts were only weakly correlated with the DEX IC (r = -.11, P < .05). Moreover, there was no statistically significant correlation between the DEX IC and circulating pro-inflammatory (CRP, IL-6, IFN-γ) or anti-inflammatory (IL-10) mediators (P > .05).
These findings challenge some prior assumptions and position this comprehensive study of glucocorticoid sensitivity as an important anchor point in the growing recognition of interindividual variation in maternal HPA axis regulation and inflammatory responses.
炎症介质与下丘脑-垂体-肾上腺（HPA）轴之间的内稳态反馈环的破坏是将慢性应激与炎症和不良健康结果（包括怀孕期间发生的结果）联系起来的关键机制。特别是，糖皮质激素敏感性的改变可能由于慢性应激而发生，包括由于种族歧视而导致的改变，并且可能与非裔美国人经历的持续不良母婴健康结果有关。虽然有一些在人类妊娠中测量细胞因子和 HPA 轴激素的大型研究，但据我们所知，没有一项研究直接在细胞水平上测量糖皮质激素敏感性，特别是在非裔美国人人群中。
我们测量了 408 名非裔美国女性妊娠早期血液样本中地塞米松（DEX）剂量反应抑制 TNF-α的全范围，并估计白细胞细胞类型对 TNF-α产生的贡献。
抑制 TNF-α产生 50%所需的平均（SD）DEX 水平（即 DEX IC ）为 9.8（5.8）nmol/L。单核细胞似乎是非抑制性 TNF-α产生的主要驱动因素，但单核细胞计数仅解释了 14%的变化。单核细胞计数与 DEX IC 的相关性较弱（r = -.11，P <.05）。此外，DEX IC 与循环促炎（CRP、IL-6、IFN-γ）或抗炎（IL-10）介质之间没有统计学上的显著相关性（P >.05）。
这些发现挑战了一些先前的假设，并将糖皮质激素敏感性的全面研究作为在不断认识到母体 HPA 轴调节和炎症反应中的个体间变异性方面的重要锚点。
