PROBLEM: 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. METHOD OF STUDY: 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. RESULTS: The mean (SD) DEX level needed to inhibit TNF-α production by 50% (ie, DEX IC50 ) 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 IC50 (r = -.11, P < .05). Moreover, there was no statistically significant correlation between the DEX IC50 and circulating pro-inflammatory (CRP, IL-6, IFN-γ) or anti-inflammatory (IL-10) mediators (P > .05). CONCLUSION: 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.
PROBLEM: 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. METHOD OF STUDY: 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. RESULTS: The mean (SD) DEX level needed to inhibit TNF-α production by 50% (ie, DEX IC50 ) 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 IC50 (r = -.11, P < .05). Moreover, there was no statistically significant correlation between the DEX IC50 and circulating pro-inflammatory (CRP, IL-6, IFN-γ) or anti-inflammatory (IL-10) mediators (P > .05). CONCLUSION: 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.
Authors: Chad A Ray; Carmen Dumaual; Mark Willey; Jeffrey Fill; Peter J O'Brien; Ian Gourley; Viswanath Devanarayan; Robert J Konrad Journal: J Pharm Biomed Anal Date: 2006-04-11 Impact factor: 3.935
Authors: Georg Varga; Jan Ehrchen; Anne Brockhausen; Toni Weinhage; Nadine Nippe; Michael Belz; Athanasios Tsianakas; Matthias Ross; Dominik Bettenworth; Tilmann Spieker; Marc Wolf; Ralph Lippe; Klaus Tenbrock; Pieter J M Leenen; Johannes Roth; Cord Sunderkötter Journal: J Immunol Date: 2014-07-02 Impact factor: 5.422