What Triggers Fatigue During Illness: Understanding the Pathophysiology?

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SUMMARY

The discussion centers on the pathophysiology of fatigue during illness, specifically focusing on the role of pyrogens like prostaglandin E2 (PGE2) in triggering fatigue and fever. It highlights that low ATP levels may contribute to fatigue, particularly in conditions like chronic fatigue syndrome, and emphasizes the involvement of inflammation during viral infections, such as COVID-19. The immune system's role, particularly through pathways involving T-cells and macrophages, is crucial in understanding fatigue mechanisms during illness.

PREREQUISITES
  • Understanding of pyrogens and their role in thermogenesis
  • Knowledge of ATP metabolism and mitochondrial function
  • Familiarity with immune system pathways, including T-cell and macrophage activation
  • Basic concepts of inflammation and its effects on the body
NEXT STEPS
  • Research the role of prostaglandin E2 (PGE2) in fatigue and fever response
  • Explore mitochondrial dysfunction in chronic fatigue syndrome
  • Investigate immune pathways involved in fatigue during viral infections
  • Study the neurobiological aspects of fatigue as outlined in relevant literature
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Researchers, healthcare professionals, and students interested in the mechanisms of fatigue during illness, particularly those studying chronic fatigue syndrome and the effects of viral infections on energy levels.

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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