Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers.

TitleGreater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers.
Publication TypeJournal Article
Year of Publication2014
AuthorsMiller GE, Murphy MLM, Cashman R, Ma R, Ma J, Arevalo JMG, Kobor MS, Cole SW
JournalBrain Behav Immun
Date Published2014 Oct
KeywordsAdult, Biomarkers, Brain Neoplasms, C-Reactive Protein, Caregivers, Cells, Cultured, Chronic Disease, Female, Gene Expression Profiling, Glioblastoma, Humans, Hydrocortisone, Inflammation, Leukocytes, Lipopolysaccharides, Male, Middle Aged, Monocytes, Receptors, Glucocorticoid, Saliva, Signal Transduction, Stress, Psychological, Transcription, Genetic

Chronic stress is associated with morbidity and mortality from numerous conditions, many of whose pathogenesis involves persistent inflammation. Here, we examine how chronic stress influences signaling pathways that regulate inflammation in monocytes. The sample consisted of 33 adults caring for a family member with glioblastoma and 47 controls whose lives were free of major stressors. The subjects were assessed four times over eight months. Relative to controls, caregivers' monocytes showed increased expression of genes bearing response elements for nuclear-factor kappa B, a key pro-inflammatory transcription factor. Simultaneously, caregivers showed reduced expression of genes with response elements for the glucocorticoid receptor, a transcription factor that conveys cortisol's anti-inflammatory signals to monocytes. Transcript origin analyses revealed that CD14+/CD16- cells, a population of immature monocytes, were the predominate source of inflammatory gene expression among caregivers. We considered hormonal, molecular, and functional explanations for caregivers' decreased glucocorticoid-mediated transcription. Across twelve days, the groups displayed similar diurnal cortisol profiles, suggesting that differential adrenocortical activity was not involved. Moreover, the groups' monocytes expressed similar amounts of glucocorticoid receptor protein, suggesting that differential receptor availability was not involved. In ex vivo studies, subjects' monocytes were stimulated with lipopolysaccharide, and caregivers showed greater production of the inflammatory cytokine interleukin-6 relative to controls. However, no group differences in functional glucocorticoid sensitivity were apparent; hydrocortisone was equally effective at inhibiting cytokine production in caregivers and controls. These findings may help shed light on the mechanisms through which caregiving increases vulnerability to inflammation-related diseases.

Alternate JournalBrain Behav. Immun.
PubMed ID25242587
PubMed Central IDPMC4973629
Grant List89736 / / Canadian Institutes of Health Research / Canada
P30 AG017265 / AG / NIA NIH HHS / United States
P30AG017265 / AG / NIA NIH HHS / United States
R24 AG037898 / AG / NIA NIH HHS / United States