What causes fatigue?

Introduction

Fatigue is a pervasive and debilitating symptom experienced across various chronic illnesses, including cancer, multiple sclerosis, chronic fatigue syndrome, and inflammatory diseases. It significantly impacts the quality of life and daily functioning of affected individuals. Understanding the underlying causes of fatigue is crucial for developing effective treatments and improving patient outcomes.

Key Insights

Inflammation and Immune Activation:
- Fatigue is often linked to increased levels of pro-inflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-alpha, which are common in chronic inflammatory diseases and cancer .
- Immune system dysregulation, including natural killer cell dysfunction and immune activation markers, is associated with chronic fatigue syndrome and other chronic illnesses .
Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation:
- Dysregulation of the HPA axis, which controls stress responses, is implicated in fatigue across various chronic conditions, including cancer, multiple sclerosis, and chronic fatigue syndrome .
Neuroinflammation and Central Nervous System (CNS) Involvement:
- Fatigue is partly generated in the brain through neuroinflammation and activation of innate immunity, with molecules like IL-1β playing a significant role .
- Neurological phenomena, including disturbances in the autonomic nervous system and cortical reorganization, contribute to fatigue in diseases like multiple sclerosis .
Mitochondrial Dysfunction and Oxidative Stress:
- Mitochondrial abnormalities and oxidative stress are linked to persistent fatigue, particularly in chronic fatigue syndrome and other chronic illnesses .
Genetic and Molecular Factors:
- Genetic predispositions and molecular mechanisms, including gene activation and epigenetic changes, are increasingly recognized as contributors to fatigue .
Muscle Fatigue and Physical Factors:
- Muscle fatigue, characterized by a decline in muscle function and energy, is often due to overtraining, deconditioning, or chronic conditions like multiple sclerosis and chronic kidney disease .
Psychosocial and Behavioral Factors:
- Psychological aspects, such as depression and anxiety, along with behavioral factors like reduced physical activity, are significant contributors to fatigue .

Conclusion

Fatigue in chronic illnesses is a multifactorial phenomenon involving inflammation, immune system dysregulation, HPA axis disturbances, neuroinflammation, mitochondrial dysfunction, genetic factors, muscle fatigue, and psychosocial elements. Addressing these diverse mechanisms is essential for developing comprehensive treatment strategies to alleviate fatigue and improve the quality of life for affected individuals.

What causes fatigue?

Summary

Introduction

Key Insights

Conclusion

Sources and full results

A Systematic Review of Biological Mechanisms of Fatigue in Chronic Illness

Fatigue in chronic illnesses like heart failure, multiple sclerosis, chronic kidney disease, rheumatoid arthritis, and chronic obstructive pulmonary disease may be linked to inflammation, the HPA axis, and the autonomic nervous system.

Fatigue in chronic inflammation - a link to pain pathways

Fatigue in inflammatory diseases, such as rheumatoid arthritis, may be linked to pain and depression, with inflammation potentially playing a common link between fatigue, pain, and depression.

Chronic fatigue syndrome: Inflammation, immune function, and neuroendocrine interactions

Chronic fatigue syndrome is linked to inflammation, immune dysfunction, and neuroendocrine interactions, with initial viral infection severity being the best predictor of persistent fatigue.

The biological basis of chronic fatigue: neuroinflammation and innate immunity.

Chronic fatigue is a complex, genetic and molecular issue triggered by neuroinflammation and innate immunity, with potential treatments focusing on proteomics, gene activation, and epigenetics.

Origin of Fatigue in Multiple Sclerosis: Review of the Literature

Fatigue in multiple sclerosis may result from multiple factors, including disease mechanisms, sleep problems, and pharmacologic treatment.

Molecular Mechanisms of Muscle Fatigue

Chronic muscle fatigue is primarily caused by muscle wasting, aging, immobilization, insulin resistance, and diseases associated with systemic inflammation, resulting in poor quality of life for affected individuals.

Cellular mechanisms of muscle fatigue.

Fatigue in muscles is primarily caused by changes in surface membrane, E-C coupling, or metabolic events, with primary sites within muscle cells and varying fiber types.

Biological mechanisms of chronic fatigue.

Chronic fatigue in autoimmune and inflammatory diseases is linked to cytokines, sickness behavior, oxidative stress, mitochondrial dysfunction, and genetic factors.

Chronic fatigue syndrome: clinical condition associated with immune activation

Immune activation is associated with many cases of chronic fatigue syndrome, but no correlation was found with known human viruses.

Cancer-related fatigue—mechanisms, risk factors, and treatments

Cancer-related fatigue is influenced by inflammation, genetic, biological, psychosocial, and behavioral factors, and can be improved through physical activity, psychosocial support, and pharmacological treatments.

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