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Does the flu shot make you are feeling sick? What this randomised trial tells us about vaccine-induced irritation

Compassionate Healer by Compassionate Healer
January 30, 2026
in Mental Health
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Does the flu shot make you are feeling sick? What this randomised trial tells us about vaccine-induced irritation
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After receiving a vaccine, you may need observed signs like muscle soreness or headache. You might also have skilled different results akin to fatigue, adjustments in temper, or feeling much less excited by assembly with folks. Possibly you might have considered all of those “unwanted effects” as a bit irritating, attempting to time your vaccine injection so it interferes as little as doable together with your day by day plans. But, these signs present that your immune system is reacting to the vaccine and thus making ready you for future encounters with pathogens.

When the immune system is activated, immune cells launch inflammatory proteins known as cytokines. These cytokines talk with the mind, which ends up in adjustments in how we really feel and behave. Such adjustments in behaviour are referred to as “illness behaviour” and embody, as an example fatigue and adjustments in social behaviour. Preventing an an infection calls for a number of vitality to gas the immune system, so illness behaviour will be seen as adaptive because it helps us protect vitality, for instance by making us wish to relaxation (Dantzer R. 2001).

Researchers use completely different experimental fashions to review how people reply to irritation. For instance, a fraction of micro organism (lipopolysaccharide, LPS) will be injected to activate the immune system, producing a robust inflammatory response for a number of hours (Lasselin J. 2025). Alternatively, vaccine fashions present an fascinating strategy to review extra delicate inflammatory adjustments and their impact on temper and habits.

Offering members with a flu shot is one vaccine mannequin used to review inflammation-induced adjustments in behaviour (Khulman Ok. R. et al., 2018). Nonetheless, we nonetheless should not have a transparent image on how a flu shot impacts completely different facets of illness behaviour. A latest examine addressed this, by conducting a randomised managed trial investigating how a vaccine injection impacts cytokine ranges in blood plasma, in addition to skilled illness behaviour (Jolink T and Feldman M. et al., 2025).

Immune activation from vaccines trigger a necessary immune response in the body, helping us build up protection for future encounters with pathogens.

Immune activation from vaccines set off a vital immune response within the physique, serving to us construct up safety for future encounters with pathogens.

Strategies

On this examine, Tatum Jolink,  Mallory Feldman and colleagues (2025) carried out a randomised, double-blind placebo-controlled trial. A complete of 52 members obtained an influenza vaccine injection, and 50 members obtained a saline injection (placebo). Simply previous to the injection, members offered a baseline blood pattern. Twenty-four hours after the injection, they returned for a second go to, throughout which they offered an extra blood pattern and accomplished a number of questionnaires assessing temper and behavior signs.

To evaluate the inflammatory response, 4 cytokines had been measured: interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). Illness habits was measured utilizing the Illness Questionnaire (SicknessQ) in addition to with two further gadgets (fatigue and muscle ache), and temper was assessed with the Optimistic and Unfavorable Have an effect on Schedule (PANAS-X). Individuals additionally answered questions on their sleep the earlier night time (i.e., first night time post-injection), and their emotions of social disconnect.

Outcomes

Individuals who obtained the influenza vaccine confirmed increased ranges of all 4 cytokines post-injection in comparison with those that obtained the placebo, indicating an inflammatory response to the flu shot. These outcomes align with earlier findings suggesting that the influenza vaccine can temporally set off the physique’s immune response (e.g., Kuhlman Ok.R. et al., 2024).

There was no important distinction between the 2 teams after the injection in temper, in how they slept the night time earlier than, or in how they felt socially related with others.  The influenza vaccine additionally didn’t induce any illness behaviour, as measured with the SicknessQ, although members who obtained the influenza vaccine did report better muscle aches in comparison with these within the placebo situation. Regardless of this, within the influenza vaccine group, participant who exhibited a bigger enhance in TNF-α post-injection, reported feeling extra drained, feeling hotter, and fewer motivated for actions.

The influenza vaccine triggered an inflammatory response, but compared to the placebo group, there were no substantial observed effects on mood or behaviour.

The influenza vaccine triggered an inflammatory response, however in comparison with the placebo group, there have been no substantial noticed results on temper or behaviour.

Conclusions

This well-controlled examine provides to the rising proof that the influenza vaccine can be utilized to review small will increase in irritation. The findings recommend that though the influenza vaccine triggered an immune response, members who obtained it didn’t report feeling sicker in comparison with the placebo group. But, a bigger enhance in TNF-α after the vaccine injection was related to sure facets of illness behaviour (e.g., tiredness).

In sum, the stronger inflammation-induced illness habits usually seen with extra intense immune challenges (e.g., Lasselin J. et al., 2021) was absent.

Although the influenza vaccine triggered an immune response, the stronger inflammation-induced sickness behavior typically observed with more intense immune challenges was absent.

Though the influenza vaccine triggered an immune response, the stronger inflammation-induced illness habits usually noticed with extra intense immune challenges was absent.

Strengths and limitations

A significant energy of this examine is that it’s the first randomised, placebo-controlled trial to research the results of an influenza vaccine on inflammatory markers in blood plasma and the way these adjustments relate to illness behaviour. The findings due to this fact strengthen the proof for utilizing the mannequin to research how delicate fluctuations in irritation can affect temper and habits. Additionally, the absence of illness behaviour in vaccinated people signifies that stronger immune challenges could also be required to review numerous facets of illness behaviour in people. That is additional supported by the affiliation between increased TNF-α ranges after the vaccine and a few facets of illness behaviour, indicating that stronger immune responses could also be wanted to set off such adjustments. This data could also be necessary for future research.

As famous by the authors, the examine pattern was restricted in each measurement and generalisability, because it consisted of younger, wholesome members. The restricted pattern measurement is especially regarding on condition that members obtained both the vaccine injection or the placebo injection. Earlier analysis signifies that folks react fairly in a different way to inflammatory challenges (e.g., Lasselin J. 2021). A within-subject design, the place members obtain the vaccine at one time and the placebo at one other time, might have been extra advantageous, as it might permit for investigation of vaccine-related adjustments in numerous self-reported elements inside every particular person.

Furthermore, though the authors discovered that the influenza vaccine elevated ranges of all measured cytokines, the info additionally present a number of variations between members. Some people didn’t present an observable enhance in each measured cytokine. Such particular person variations are fascinating and could possibly be checked out extra carefully in future research.

A energy of the examine is that it examined how the influenza vaccine impacts a number of facets akin to signs, social experiences, sleep, and temper. Nonetheless, a limitation is that all outcomes had been self-reported. Earlier analysis utilizing the influenza vaccine has urged that this mannequin could also be notably well-suited for learning computerized behaviours (Jolink T. et al., 2022). These behaviours are implicit, as illustrated by measurements such because the response time required for a participant to maneuver away from an object or one other particular person. The current randomised managed trial might due to this fact have benefited from combining subjective and goal outcomes, which might assist to additional make clear how this vaccine mannequin differs from stronger immune challenges, and for which analysis functions it could be greatest suited. For instance, future research might embody each self-reported and objectively measurable sleep high quality or evaluate self-reported illness signs with observable expressions of illness.

This study supports the use of vaccine models to explore inflammation’s subtle effects but highlights key design and measurement limitations that must be address in future studies.

This examine helps using vaccine fashions to discover irritation’s delicate results, however highlights key design and measurement limitations that should be deal with in future research.

Implications for follow

After studying this submit, it’s doable that your subsequent vaccine shot shall be adopted by ideas of which signs which will observe. If it’s a flu shot, the offered proof signifies that though your immune system shall be activated, chances are you’ll not really feel in a different way. But, as additionally famous by the authors, extra research with bigger and extra numerous samples are wanted to completely perceive how influenza vaccines have an effect on us.

Understanding how the “dose” of irritation pertains to completely different facets of illness behaviour is necessary to make clear the perform and doable adaptiveness of those behavioral adjustments (Lindsay, 2022). For instance, a gentle inflammatory problem might alter your behaviour in an implicit means, akin to elevated social strategy in the direction of shut others (Jolink T. et al., 2022). In distinction, a robust activation of the immune system could also be required so that you can explicitly categorical a necessity for care (Hansson L. et al., 2024). Understanding these variations can assist us higher grasp inflammation-related well being circumstances and enhance care. For example, if care-seeking behaviors are solely triggered as soon as irritation reaches a sure threshold, this could possibly be necessary in well being care settings.

Though the irritation brought on by a vaccine injection is adaptive and short-term, serving to us construct safety for future encounters with pathogens, long-term persistent irritation will be maladaptive. Power irritation is a well-recognised threat issue for a number of psychological well being circumstances, together with despair and schizophrenia (you possibly can learn extra about this in these Psychological Elf blogs on irritation). Though the influenza vaccine didn’t considerably have an effect on the habits or temper measures assessed right here, earlier analysis has demonstrated acute results on social behaviour (Jolink T. et al., 2022) and depressive signs (Khulman Ok. R. et al., 2018). Thus, this mannequin can be utilized to assist us perceive the mechanisms by which irritation contributes to completely different psychological well being circumstances.

This study supports the use of vaccine models to explore inflammation’s subtle effects but highlights key design and measurement limitations that must be address in future studies.

This examine helps using vaccine fashions to discover irritation’s delicate results however highlights key design and measurement limitations that should be deal with in future research.

Assertion of pursuits

Dr. Muscatell was the opponent at my doctoral defence, and we now have mentioned and submitted a funding software for future collaborations. I used ChatGPT-5 to assist test the grammar and to enhance the readability and the model of my preliminary draft.

Editor

Edited by Éimear Foley. AI instruments assisted with language refinement and formatting throughout the editorial section.

Hyperlinks

Major paper

Jolink, T.A., Feldman, M.J., Antenucci, N.M., Cardenas, M.N., West, T.N., Nakamura, Z.M., Muscatell, Ok.A., 2025. Results of a gentle inflammatory problem on cytokines and illness habits: A randomized managed trial utilizing the influenza vaccine. Mind. Behav. Immun. 128, 429–439. https://doi.org/10.1016/j.bbi.2025.04.018

Different references
Dantzer, R., 2001. Cytokine-Induced Illness Conduct: The place Do We Stand? Mind. Behav. Immun. 15, 7–24. https://doi.org/10.1006/brbi.2000.0613

Hansson, L.S., Tognetti, A., Sigurjónsson, P., Brück, E., Wåhlén, Ok., Jensen, Ok., Olsson, M.J., Toll John, R., Wilhelms, D.B., Lekander, M., Lasselin, J., 2024. Notion of unfamiliar caregivers throughout illness – Utilizing the brand new Caregiver Notion Job (CgPT) throughout experimental endotoxemia. Mind. Behav. Immun. 119, 741–749. https://doi.org/10.1016/j.bbi.2024.04.031

Jolink, T.A., Fendinger, N.J., Alvarez, G.M., Feldman, M.J., Gaudier-Diaz, M.M., Muscatell, Ok.A., 2022. Inflammatory reactivity to the influenza vaccine is related to adjustments in computerized social habits. Mind. Behav. Immun. 99, 339–349. https://doi.org/10.1016/j.bbi.2021.10.019

Kuhlman, Ok.R., Radin, A., Cole, S.W., Bower, J.E., 2024. Psychosocial predictors of the innate immune response to influenza vaccination. Psychoneuroendocrinology 163, 106989. https://doi.org/10.1016/j.psyneuen.2024.106989

Kuhlman, Ok.R., Robles, T.F., Dooley, L.N., Boyle, C.C., Haydon, M.D., Bower, J.E., 2018. Inside-subject associations between irritation and options of despair: Utilizing the flu vaccine as a gentle inflammatory stimulus. Mind. Behav. Immun. 69, 540–547. https://doi.org/10.1016/j.bbi.2018.02.001

Lasselin, J., 2025. Placing oil on the fireplace: Do folks with excessive irritation react in a different way to immune stress? The Psychological Elf.

Lasselin, J., 2021. Again to the way forward for psychoneuroimmunology: Finding out inflammation-induced illness habits. Mind Behav. Immun. – Well being 18, 100379. https://doi.org/10.1016/j.bbih.2021.100379

Lasselin, J., Lekander, M., Benson, S., Schedlowski, M., Engler, H., 2021. Sick for science: experimental endotoxemia as a translational software to develop and take a look at new therapies for inflammation-associated despair. Mol. Psychiatry 26, 3672–3683. https://doi.org/10.1038/s41380-020-00869-2

Lindsay, E.Ok., 2022. Small “doses” of irritation provoke social illness habits. Mind. Behav. Immun. 102, 40–41. https://doi.org/10.1016/j.bbi.2022.02.012

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