December 11, 2008Open Access
Chronic Interpersonal Stress Predicts Activation of Pro- and Anti-Inflammatory Signaling Pathways 6 Months Later
Key Result
Higher baseline chronic interpersonal stress in healthy young women predicted greater increases in mRNA for NF-kappaB and pronounced IL-6 responses to microbial challenge over 6 months.
Study Design
Type
Cohort (n=103)
Structured PICO
Does chronic interpersonal stress increase pro- and anti-inflammatory signaling pathways in healthy young women?
P
Population
103 healthy young women (mean age 17 years) followed for 6 months to assess the impact of chronic interpersonal stress on inflammatory signaling pathways.
E
Exposure
High chronic interpersonal stress (assessed via structured interview)
C
Comparator
Lower levels of chronic interpersonal stress
O
Outcome
Changes in systemic inflammation, expression of signaling molecules (mRNA for NF-kappaB and inhibitor of kappaB), and leukocyte production of interleukin-6 after ex vivo stimulation with lipopolysaccharide at 6 monthssurrogate
Chronic interpersonal stress accentuates the expression of pro- and anti-inflammatory signaling molecules and the inflammatory response to microbial challenge, potentially contributing to inflammation-sensitive diseases like atherosclerosis.
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-kappaB (NF-kappaB) over the next 6 months. They also showed larger increases in mRNA for inhibitor of kappaB, a molecule that sequesters NF-kappaB 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.