Chronic fatigue syndrome/myalgic encephalomyelitis (CFS) is a complex, multisystem disease that is characterized by long-term fatigue, exhaustion, disabilities, pain, neurocognitive impairments, gastrointestinal symptoms, and post-exertional malaise, as well as lowered occupational, educational, and social functions. The clinical and biomarker diagnosis of this disorder is hampered by the lack of validated diagnostic criteria and laboratory tests with adequate figures of merit, although there are now many disease biomarkers indicating the pathophysiology of CFS. Here, we review multiple factors, such as immunological and environmental factors, which are associated with CFS and evaluate current concepts on the involvement of immune and environmental factors in the pathophysiology of CFS. The most frequently reported immune dysregulations in CFS are modifications in immunoglobulin contents, changes in B and T cell phenotypes and cytokine profiles, and decreased cytotoxicity of natural killer cells. Some of these immune aberrations display a moderate diagnostic performance to externally validate the clinical diagnosis of CFS, including the expression of activation markers and protein kinase R (PKR) activity. Associated with the immune aberrations are activated nitro-oxidative pathways, which may explain the key symptoms of CFS. This review shows that viral and bacterial infections, as well as nutritional deficiencies, may further aggravate the immune-oxidative pathophysiology of CFS. Targeted treatments with antioxidants and lipid replacement treatments may have some clinical efficacy in CFS. We conclude that complex interactions between immune and nitro-oxidative pathways, infectious agents, environmental factors, and nutritional deficiencies play a role in the pathophysiology of CFS.

慢性疲劳综合征/肌性脑脊髓炎（CFS）是一种复杂的多系统疾病，其特征在于长期疲劳，疲惫，残疾，疼痛，神经认知障碍，胃肠道症状和劳累乏力，以及职业，教育，和社会功能。该疾病的临床和生物标志物诊断因缺乏有效的诊断标准和实验室测试而无法获得足够的评价，尽管现在有许多疾病生物标志物表明了CFS的病理生理。在这里，我们回顾了与CFS相关的多种因素，例如免疫学和环境因素，并评估了CFS病理生理学中涉及免疫和环境因素的最新概念。CFS中最常报告的免疫失调是免疫球蛋白含量的改变，B和T细胞表型和细胞因子谱的变化以及天然杀伤细胞的细胞毒性降低。这些免疫畸变中的某些表现出适度的诊断性能，以从外部验证CFS的临床诊断，包括激活标志物的表达和蛋白激酶R（PKR）活性。与免疫异常相关的是激活的硝基氧化途径，这可能解释了CFS的关键症状。这项审查表明，病毒和细菌感染以及营养缺乏症可能进一步加重CFS的免疫氧化病理生理。抗氧化剂的靶向治疗和脂质替代治疗可能在CFS中具有一定的临床疗效。