Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans
Open accessAbstract
Activation of the innate immune system is commonly accompanied by a set of behavioural, psychological and physiological changes known as 'sickness behaviour'. In animals, infection-related sickness symptoms are significantly increased by exposure to psychosocial stress, suggesting that psychological and immune stressors may operate through similar pathways to induce sickness. We used a double-blind, randomised, placebo-controlled design to examine the effect of acute psychological stress on immune and subjective mood responses to typhoid vaccination in 59 men. Volunteers were assigned to one of four experimental conditions in which they were either injected with typhoid vaccine or saline placebo, and then either rested or completed two challenging behavioural tasks. Typhoid vaccine induced a significant rise in participants' serum levels of interleukin-6 (IL-6) and this response was significantly larger in the stress versus rest conditions. Negative mood increased immediately post-tasks, an effect also more pronounced in the vaccine/stress condition. In the vaccine/stress group, participants with larger IL-6 responses had heightened systolic blood pressure responses to tasks and elevated post-stress salivary levels of the noradrenaline metabolite 3-methoxy-phenyl glycol (MHPG) and cortisol. Our findings suggest that, as seen in animals, psychological and immune stressors may act synergistically to promote inflammation and sickness behaviour in humans.
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Typhoid vaccination caused greater negative mood following two stress tasks compared to placebo, driven by increases in fatigue and confusion.
“Typhoid vaccination caused greater negative mood following two stress tasks (a Stroop color-word task and a simulated public speaking exercise) compared to a placebo group; elevations in negative mood were driven by increases in fatigue and confusion (Brydon et al., 2009).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2009
Participants with larger vaccine-induced IL-6 responses exhibited elevated systolic blood pressure responses to stress tasks, as well as elevated post-stress cortisol and a marker of noradrenaline.
“Additionally, participants with larger vaccine-induced IL-6 responses exhibited elevated systolic blood pressure responses to stress tasks, as well as elevated post-stress cortisol and a marker of noradrenaline (Brydon et al., 2009).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2009
Typhoid vaccination increases subjective ratings of mental confusion and impaired concentration.
“Typhoid vaccination increases subjective ratings of mental confusion and impaired concentration (Brydon et al., 2009; Harrison et al., 2009).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2009
Studies using IFN-α and typhoid vaccination have found that inflammation increases are associated with subjective cognitive complaints.
“Further, IFN-α and typhoid studies have documented links between increases in inflammation and subjective cognitive complaints (Brydon et al., 2009; Capuron et al., 2002; Harrison et al., 2009).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2009
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- Authors
- Brydon, L., Walker, C., Wawrzyniak, A., Whitehead, D., Okamura, H., Yajima, J., Tsuda, A., & Steptoe, A.
- Affiliations
- University College London (GB)
- Kurume University (JP)
- Corresponding author
- Brydon, Lena
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 23
- Issue
- 2
- Pages
- 217-224
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC2637301
- OpenAlex
- W2068664197
- Cited by
- 164
- References
- 39
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 9 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 14 · 2013: 16 · 2012: 15
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- British Heart Foundation
- Japan Society for the Promotion of Science (21300252)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- sickness behavior, psychological stress, immune stress, interleukin-6, typhoid vaccination, inflammation, negative mood, blood pressure, cortisol, innate immunity, psychoneuroimmunology
- MeSH terms
- Adolescent, Adult, Affect, Blood Pressure, Double-Blind Method, Enzyme-Linked Immunosorbent Assay, Humans, Hydrocortisone, Injections, Intramuscular, Male, Methoxyhydroxyphenylglycol, Neuropsychological Tests, Placebos, Psychomotor Performance, Saliva, Stress, Psychological, Typhoid-Paratyphoid Vaccines, Neuroimmunomodulation, Interleukin-6, Cytokines, Illness Behavior, Young Adult
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