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Acute inflammation and negative mood: Mediation by cytokine activation
Abstract
Inflammatory diseases are commonly associated with depressed mood. This association may be influenced by the production of proinflammatory cytokines. Accordingly, we assessed whether cytokine levels and mood (measured with the profile of mood states) could be altered by a mild, non-sickness inducing, acute inflammatory stimulus. Using a randomised placebo-controlled, double-blind design, 30 healthy male volunteers were injected with Salmonella typhi vaccine or placebo. Assessments of mood, symptoms of illness and temperature were made at baseline and at 1.5, 3, and 6 h post-injection. Plasma concentrations of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and tumour necrosis factor-alpha (TNF-alpha) were assessed at baseline and 3 h post-injection. No significant symptoms of illness were reported in either group. Mood was more negative following injection in the vaccine than the placebo group, and the vaccine group experienced a 106% increase in IL-6 concentration. Negative changes in mood following injection were significantly correlated with increases in IL-6 production. No changes in TNF-alpha or IL-1Ra concentration were recorded in either group. It is concluded that S. typhi vaccination may be a useful model of mild inflammatory challenge, producing a significant transient cytokine-induced decrease in mood in the absence of any febrile response. Implications for depressed mood in physical illness are discussed.
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In the citing paper
“typhoid vaccination, which is a relatively mild inflammatory challenge, elicits significant increases in negative mood, confusion, and fatigue, and these effects are mediated by changes in IL-6”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as C. E. Wright, Strike, Brydon, & Steptoe, 2005
In the citing paper
“Results from such studies have shown that typhoid vaccination can lead to symptoms relevant to depression, including negative mood, fatigue, and confusion (Harrison et al., 2009; Wright et al., 2005).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Wright et al., 2005
In the citing paper
“Typhoid vaccination leads to a modest, short-term inflammatory response; for example, an average increase of 0.82 pg/mL (a 106% increase) in IL-6 at 3 hours post-vaccination (Wright et al., 2005) and increases in inflammation resolve within 24 hours following typhoid vaccination (Paine et al., 2013).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Wright et al., 2005
In the citing paper
“Studies across the endotoxin, typhoid vaccination, and IFN-α paradigms have consistently shown that exogenous stimulation of proinflammatory cytokines leads to reports of increased fatigue (Brydon et al., 2008; Capuron et al., 2002; Dowell et al., 2016; Eisenberger et al., 2010a; Grigoleit et al., 2011; Harrison et al., 2009; Moieni et al., 2015) and decreases in ratings of vigor (Dowell et al., 2”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Wright et al., 2005
In the citing paper
“Associations between circulating IL-6 levels and negative mood have been reported previously [28], [62] and IL-6 frequently has been discussed as a potential modulator of mood during sickness behavior and even depression and other neuropsychological diseases [2], [3], [9].”
From Dose-dependent effects of endotoxin on neurobehavioral functions in humans (2011) · cites this paper as [62]
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Metadata
- Authors
- Wright, C. E., Strike, P. C., Brydon, L., & Steptoe, A.
- Affiliations
- University College London (GB)
- Corresponding author
- Wright, C.E.
- Steptoe, A.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 19
- Issue
- 4
- Pages
- 345-350
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2024917272
- Cited by
- 287
- References
- 31
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 16 · 2023: 15 · 2022: 13 · 2021: 7 · 2020: 7 · 2019: 17 · 2018: 28 · 2017: 14 · 2016: 24 · 2015: 20 · 2014: 9 · 2013: 16 · 2012: 14
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- British Heart Foundation
- Fondation pour la Recherche Médicale
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- acute inflammation, negative mood, depressive mood, inflammatory cytokines, interleukin-6, interleukin-1 receptor antagonist, TNF-α, disease symptoms, body temperature, mediation
- MeSH terms
- Acute Disease, Adult, Affect, Affective Symptoms, Analysis of Variance, Depression, Double-Blind Method, Humans, Inflammation, Male, Reference Values, Salmonella typhi, Sialoglycoproteins, Sick Role, Tumor Necrosis Factor-alpha, Typhoid-Paratyphoid Vaccines, Interleukin-6, Cytokines, Interleukin 1 Receptor Antagonist Protein
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