Chronic Interpersonal Stress Predicts Activation of Pro- and Anti-Inflammatory Signaling Pathways 6 Months Later
- 1 January 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Psychosomatic Medicine
- Vol. 71 (1), 57-62
- https://doi.org/10.1097/psy.0b013e318190d7de
Abstract
Objective: To understand the mechanisms underlying chronic interpersonal difficulties and their detrimental influence on mental and physical health. Methods: A total of 103 healthy young women (mean age = 17 years) were administered a structured interview to assess the degree of chronic interpersonal stress in their lives. At the same time, blood was drawn to measure systemic inflammation, the expression of signaling molecules that regulate immune activation, and leukocyte production of the cytokine interleukin-6 after ex vivo stimulation with lipopolysaccharide. All of the immunologic assessments were repeated 6 months later. Results: To the extent subjects were high in chronic interpersonal stress at baseline, their leukocytes displayed greater increases in messenger ribonucleic acid (mRNA) for the proinflammatory transcription factor nuclear factor-κB (NF-κB) over the next 6 months. They also showed larger increases in mRNA for inhibitor of κB, a molecule that sequesters NF-κB in the cytoplasm and minimizes its proinflammatory activities. Chronic interpersonal stress at baseline was unrelated to changes in biomarkers of systemic inflammation but was associated with increasingly pronounced interleukin-6 responses to lipopolysaccharide. These associations were independent of demographics, lifestyle variables, and depressive symptoms. Conclusions: These findings suggest that chronic interpersonal difficulties accentuate expression of pro- and anti-inflammatory signaling molecules. Although this process does not result in systemic inflammation under quiescent conditions, it does accentuate leukocytes’ inflammatory response to microbial challenge. These dynamics may underlie the excess morbidity associated with social stress, particularly in inflammation-sensitive diseases like depression and atherosclerosis. CRP = C-reactive protein; GR = glucocorticoid receptor; IκB = inhibitor of κB; IL = interleukin; mRNA = messenger ribonucleic acid; NF-κB = nuclear factor-κB.This publication has 38 references indexed in Scilit:
- A Functional Genomic Fingerprint of Chronic Stress in Humans: Blunted Glucocorticoid and Increased NF-κB SignalingBiological Psychiatry, 2008
- From inflammation to sickness and depression: when the immune system subjugates the brainNature Reviews Neuroscience, 2008
- Psychological Stress and DiseaseJama-Journal Of The American Medical Association, 2007
- Social regulation of gene expression in human leukocytesGenome Biology, 2007
- Neural regulation of innate immunity: a coordinated nonspecific host response to pathogensNature Reviews Immunology, 2006
- Cytokines sing the blues: inflammation and the pathogenesis of depressionTrends in Immunology, 2006
- Metabolic SyndromeCirculation, 2005
- Neuroendocrine Regulation of ImmunityAnnual Review of Immunology, 2002
- Risky families: Family social environments and the mental and physical health of offspring.Psychological Bulletin, 2002
- Generation of stress in the course of unipolar depression.Journal of Abnormal Psychology, 1991