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Evaluating the Role of Mitochondrial Function in Cancer-related Fatigue

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Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms.

S Mechiel Korte^1,2, Rainer H Straub³

¹Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, (UIPS), Utrecht University, Utrecht, The Netherlands.

Rheumatology (Oxford, England)

|November 5, 2019

Summary

Inflammatory rheumatic disorders cause persistent fatigue through complex pathophysiological mechanisms. Proinflammatory cytokines and oxidative stress disrupt neurotransmitter balance, impacting brain function and leading to fatigue.

Keywords:

fatigue inflammation mechanisms pathophysiology rheumatic disorders

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Area of Science:

Neuroscience
Immunology
Rheumatology

Background:

Rheumatic disorders are treatable, yet residual fatigue persists in many patients.
Understanding the mechanisms of fatigue is crucial for improving patient outcomes.

Purpose of the Study:

To elucidate the pathophysiological mechanisms underlying fatigue in inflammatory rheumatic disorders.
To identify key molecular and cellular pathways contributing to persistent fatigue.

Main Methods:

Review of current literature on cytokine signaling and neurotransmitter metabolism.
Analysis of the impact of chronic inflammation on monoaminergic and glutamatergic systems.
Investigation of the role of oxidative stress and astrocyte function in fatigue.

Main Results:

Proinflammatory cytokines disrupt neurotransmitter release and increase monoamine breakdown.
Oxidative stress and increased indoleamine-2,3-dioxygenase activity reduce serotonin availability.
Astrocytes contribute to fatigue by inhibiting neurotransmitter transporters and producing kynurenic acid, which reduces dopamine release.

Conclusions:

Fatigue in rheumatic disorders stems from complex interactions between inflammation, oxidative stress, and neurotransmitter dysregulation.
These mechanisms collectively impair brain function in fatigue-related areas.
Targeting these pathways may offer novel therapeutic strategies for managing fatigue.