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Effects of a mild inflammatory challenge on cytokines and sickness behavior: A randomized controlled trial using the influenza vaccine. | LitMetric

Effects of a mild inflammatory challenge on cytokines and sickness behavior: A randomized controlled trial using the influenza vaccine.

Brain Behav Immun

University of North Carolina at Chapel Hill, Department of Psychology & Neuroscience, United States; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, United States; Carolina Population Center, University of North Carolina at Chapel Hill, United States.

Published: August 2025


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Article Abstract

The influenza vaccine has reliably been associated with mild, within-person increases in inflammation. However, the field lacks rigorous experimental work comparing the effects of the influenza vaccine to a placebo control on changes in plasma inflammatory cytokines and self-reported sickness behavior. In a double-blind, randomized, placebo-controlled trial, 102 participants received either the influenza vaccine or saline placebo. Four cytokines were measured in plasma 24-hours following injection; participants also reported on psychosocial outcomes, specifically sickness behavior, positive/negative affect, sleep, and subjective social disconnection. All cytokines-IL-6, IL-10, TNF-α, IFN-γ-were significantly increased in the influenza vaccine condition compared to placebo. None of the psychosocial outcomes differed by condition. This study fills a gap in the literature by presenting critical causal evidence that the influenza vaccine leads to elevated levels of four inflammatory cytokines, compared to placebo control. However, a more robust increase in inflammation or a larger sample size may be necessary to observe differences in self-reported sickness behavior and other psychosocial outcomes.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286727PMC
http://dx.doi.org/10.1016/j.bbi.2025.04.018DOI Listing

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