The immune system plays a crucial role in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), with immune dysfunction being a significant factor in the disease’s pathology. Research has shown that individuals with ME/CFS often exhibit abnormalities in immune cell metabolism, particularly in CD4+ and CD8+ T cells, which are essential for immune response. These cells show disruptions in energy production, leading to reduced glycolysis and mitochondrial dysfunction. Additionally, immune system irregularities, such as altered cytokine profiles and increased autoimmunity, contribute to chronic inflammation and the persistence of symptoms. These findings highlight the complex interplay between the immune system and ME/CFS, suggesting that immune dysfunction may be a key driver of the disease.

Nervous and cardiovascular system changes are often responsible for many of the debilitating symptoms seen with ME/CFS, such as fatigue and exercise intolerance. Research shows that patients with ME/CFS often experience autonomic nervous system dysfunction, affecting bodily functions such as heart rate and blood pressure. In addition, cardiovascular irregularities, such as higher daytime heart rates and reduced heart rate variability suggest that the heart's natural pacemaker may not be functioning at optimal levels.

Changes in the endocrine system are believed to play a significant role in the development and persistence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Research indicates that individuals with ME/CFS often exhibit dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is crucial for stress response and energy regulation. This dysregulation can lead to abnormal levels of cortisol, a hormone essential for managing stress and inflammation. Additionally, imbalances in other hormones such as thyroid hormones, growth hormones, and sex hormones have been observed, contributing to the widespread symptoms of fatigue, cognitive impairment, and pain associated with ME/CFS.

Metabolic and mitochondrial dysfunction are increasingly recognized as significant contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Mitochondria, the powerhouses of cells, are responsible for producing ATP, the primary energy currency of the body. In individuals with ME/CFS, studies have shown abnormalities in mitochondrial function, particularly in the electron transport chain, which is crucial for ATP production. These dysfunctions can lead to reduced energy availability, contributing to the profound fatigue experienced by ME/CFS patients. Additionally, metabolic dysregulation, including altered levels of metabolites and phospholipids, has been observed, indicating that the body’s energy production and utilization processes are impaired. This combination of metabolic and mitochondrial dysfunction not only affects energy levels but also contributes to other symptoms such as cognitive impairment, muscle pain, and post-exertional malaise.

Viral persistence and viral reactivation are thought to play a significant role in the development and exacerbation of ME/CFS. After an initial viral infection, certain viruses, such as human herpesviruses (EBV, HHV-6, etc.) and enteroviruses, can remain dormant in the body. Under conditions of immune dysfunction or stress, these latent viruses may reactivate, leading to chronic inflammation and immune dysregulation. This reactivation can contribute to the wide array of symptoms seen in ME/CFS, including severe fatigue, cognitive impairment, and muscle pain.