Effects of Psychological Stress on Glucocorticoid Sensitivity of Inflammatory Response to Influenza Vaccine Challenge in Healthy Military College Students
Background: Influenza and other infectious diseases are critical barriers to the health and readiness of military units worldwide with reported rates of annual influenza infection as high as 45%. Vaccination to prevent infections stimulates a transient, inflammatory response, counterbalanced by the anti-inflammatory effects of increased cortisol secretion which enhances antibody production for seroprotection. Paradoxically, chronically-stressed individuals have elevated cortisol levels, but have poorer antibody response to vaccination. Evidence suggests that chronic stress impairs immune cell glucocorticoid sensitivity (GCS), leading to excessive production of proinflammatory cytokines. This pathway may contribute to impaired immune responses to vaccination and increased risk of infectious illness in military personnel in high stress areas of service.Purpose: The study was conducted to determine if psychological stress diminishes GCS and regulation of proinflammatory cytokine production in a population of healthy military students and personnel. It is hypothesized that subjects with greater psychological stress will have lower GCS in an ex vivo laboratory model of influenza vaccine challenge.Methods: A cross sectional design was used with a convenience sample of healthy, military college students and personnel (n = 61). Subjects completed the Perceived Stress Scale (PSS) and trait subscale portion of the State-Trait Anxiety Inventory (STAI-T) as measures of psychological stress and provided a blood sample. Whole blood was incubated in the presence of influenza vaccine and dexamethasone to evaluate cytokine production and GCS. Associations between psychological stress and cytokine production were evaluated using correlation and linear regression.Results: Pearson correlations, Analysis of Variance (ANOVA) with post-hoc Dunnett's T3 procedure, and Multiple Regressions were utilized for statistical analyses. PSS and vaccine-stimulated cytokine production were not significantly correlated. One-way ANOVA and post-hoc Dunnett's T3 Test revealed significant differences in cytokine concentrations in the 3 ex vivo conditions (i.e., Unstimualted, Vaccine-stimulated, and DEX-inhibited) (p<0.001). Results of the Pearson correlations showed that PSS scores were inversely related to GCS (p<0.05) for all 4 vaccine-stimulated cytokines. Finally, multiple regression models controlling for age, gender, race, and student cumulative grade point average (GPA) revealed a negative relationship between PSS and GCS of vaccine-stimulated production of IL-1ß (ß = -0.420, t = -3.55, p<0.01), IL-6 (ß = -0.296, t = -2.36, p<0.05), and TNF-a (ß = -0.259, t = -2.060, p<0.05), but not IFN-y.Conclusions: Findings from this study suggest a biologic pathway through which perceived psychological stress might alter the inflammatory immune response to influenza vaccination and expand understanding of how stress might impact immune function in military populations.
Endocrinology, Health Sciences, Immunology, Neurobiology, Nursing, Physiology, Psychobiology, Armed Forces, Inflammatory response, Influenza virus vaccination, Vaccine, Flu shot, Psychoneuroimmunology (PNI), Psychological Stress, Glucocorticoids, Glucocorticoid Sensitivity, Glucocorticoid Resistance, Military, College Students, Stress
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