What Triggers Fatigue During Illness: Understanding the Pathophysiology?

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Discussion Overview

The discussion centers on the mechanisms and pathophysiology of fatigue during illness, particularly focusing on the triggers and biological processes that lead to physical and mental fatigue. Participants explore various factors, including inflammation, mitochondrial dysfunction, and immune system involvement, in the context of both acute and long-term fatigue following viral infections.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • One participant inquires about the sequence of events that lead to fatigue during illness, specifically referencing the role of pyrogens like prostaglandin E2 (PGE2) in triggering fever and its potential connection to fatigue.
  • Another participant suggests that low ATP levels might underlie fatigue, linking it to mitochondrial dysfunction, particularly in chronic fatigue syndrome.
  • There is a mention of the role of inflammation in fatigue during and after viral infections, with specific reference to COVID-19 and the phenomenon of long COVID.
  • Questions are raised about the immune system's involvement in fatigue, particularly regarding specific immune pathways such as T-cell and macrophage activation.
  • Several participants share references to research articles that may provide additional insights into the neurobiological aspects of fatigue and its relation to immune responses.

Areas of Agreement / Disagreement

Participants express various hypotheses regarding the causes of fatigue during illness, but no consensus is reached. Multiple competing views on the mechanisms involved remain present, particularly concerning the roles of inflammation, mitochondrial function, and immune system pathways.

Contextual Notes

Some discussions highlight limitations in current understanding, such as the need for further exploration of specific immune pathways and the complexity of fatigue as a symptom that may vary across different illnesses.

Who May Find This Useful

This discussion may be of interest to researchers and practitioners in the fields of immunology, neurology, and chronic illness, as well as individuals seeking to understand the biological underpinnings of fatigue during illness.

mktsgm
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TL;DR
What events trigger fatigue during an illness and how?
What is the mechanism of Fatigue what events initiate it and how?

[CODE title="The wikipedia definition of Fever"]The trigger of a fever, called a pyrogen, results in the release of prostaglandin E2 (PGE2)[/CODE]

Generally just as a pyrogen such as PGE2 (or LPS) sets thermogenesis in motion, leading to a fever, what kind of events are triggered in physical and mental fatigue during an illness?

I want to know the basic pathophysiology or the sequence of events that are triggered to cause fatigue or tiredness during an illness.

Thanks in advance,
 
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What research have you done on this yourself? What have you found?
 
phinds said:
What research have you done on this yourself? What have you found?
By fatigue, I mean the feeling of loss of energy.

Since ATP is the currency of energy, low ATP levels may be the underlying reason for fatigue.

Normally, as in a chronic fatigue syndrome, mitochondrial dysfunction may be suspected.

After going through a lot of NCBI articles on fatigue, I think this article gave me overall input on fatigue

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136529/

But, I feel during an illness (especially during/after a viral infection) somehow the process of inflammation may also be involved in fatigue and malaise.

In the Covid situation, for example, some had fever and fatigue/malaise during acute phase and some later had fatigue-only continuing for months, as long covid. Fatigue is found common both in acute and long covid. It is common in all other illnesses too.

So, I want to know how the immune system is involved in fatigue during an illness? Is any particular immune pathway (like complement, T-cell, macrophage activation) more involved in fatigue during an illness? If so, what and how, also...
 
Last edited:
Not what you are asking, but here's another reference that may be related.

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001643
Adverse effects following anti-COVID-19 vaccination with mRNA-based BNT162b2 are alleviated by altering the route of administration and correlate with baseline enrichment of T and NK cell genes.
Syenina A, Gan ES, Toh JZN, de Alwis R, Lin LZ, Tham CYL, Yee JX, Leong YS, Sam H, Cheong C, the YE, Wee ILE, Ng DHL, Chan KR, Sim JXY, Kalimuddin S, Ong EZ, Low JG, Ooi EE.

"Herein, we found that higher baseline expression of genes related to T and NK cell exhaustion and suppression were positively correlated with the development of moderately severe fatigue after Pfizer-BioNTech BNT162b2 vaccination; increased expression of genes associated with T and NK cell exhaustion and suppression reacted to vaccination were associated with greater levels of innate immune activation at 1 day postvaccination."
 

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