The effect of a transient immune activation on subjective health perception in two placebo controlled randomised experiments

Anna Andreasson*, Bianka Karshikoff, Lisa Lidberg, Torbjörn Åkerstedt, Martin Ingvar, Caroline Olgart Höglund, John Axelsson, Mats Lekander

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
3 Downloads (Pure)


Background: Patient-reported outcomes predict mortality and play increasingly important roles in care, but factors that modify central measures such as health ratings have been little investigated. Building on designated immune-to-brain pathways, we aimed to determine how a short-term induced inflammation response impacts self-reported health status. Methods: Lipopolysaccharide injections were used to provoke acute systemic inflammatory responses in healthy men and women and were compared to placebo in two double-blind randomized experiments. In Experiment 1, 8 individuals (mean 24 years; SD = 3.7) received lipopolysaccharide 0.8 ng/kg once and placebo once in a cross-over design, and in Experiment 2, 52 individuals received either lipopolysaccharide 0.6 ng/kg or placebo once (28.6 years; SD = 7.1). Main outcomes were perceived health (general and current), sickness behaviour (like fatigue, pain and negative affect), and plasma interleukin-6, interleukin-8 and tumour necrosis factor-α, before and after injection. Results: Compared to placebo, lipopolysaccharide lead to a deterioration in both self-rated general (Experiment 1, b = 1.88 for 0.8 ng/kg) and current health (Experiment 1 b = -3.00; and Experiment 2 b = -1.79) 1.5h after injection (p’s<0.01), effects that remained after 4.5 to 5 hours (p’s<0.05). The effect on current health in Experiment 2 was mediated by increased inflammation and sickness behaviour in response to lipopolysaccharide injection (β = -0.28, p = 0.01). Conclusion: Health is drastically re-evaluated during inflammatory activation. The findings are consistent with notions that inflammation forms part of health-relevant interoceptive computations of bodily state, and hint at one mechanism as to why subjective health predicts longevity.

Original languageEnglish
Article numbere0212313
Number of pages13
JournalPLoS ONE
Issue number3
Publication statusPublished - 6 Mar 2019
Externally publishedYes

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Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


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