Effects of a mild inflammatory challenge on cytokines and sickness behavior: A randomized controlled trial using the influenza vaccine, 2025, Jolink+

Effects of a mild inflammatory challenge on cytokines and sickness behavior: A randomized controlled trial using the influenza vaccine
Jolink; Feldman; Antenucci; Cardenas; West; Nakamura; Muscatell

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.

HIGHLIGHTS
• Ran double-blind, randomized, placebo-controlled trial with the influenza vaccine.

• All cytokines—IL-6, IL-10, TNF-a, IFN-g—significantly increased in flu group (v placebo)

• No condition effects on reported sickness behavior, e.g., symptoms or sleep.

• No condition effects on state affect or reports of social disconnection.

• May need greater increase in inflammation to cause changes in self-report outcomes.

Link (Brain, Behavior, and Immunity)

 

Posted in relation to discussion on flu/myalgia in the thread A Thought Experiment on Muscles.