Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger.
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.
Curr Opin Neurol. 2020 Jun;33(3):391-396. doi: 10.1097/WCO.0000000000000817.
Chronic fatigue is common in cancer, neurodegenerative, and chronic inflammatory diseases and is regarded by many patients as their absolutely worst problem. Lately, fatigue is increasingly understood to have a genetic and molecular basis.
Biologically, fatigue occurs as part of the sickness behavior response, a complex and automated behavior triggered by the activation of innate immunity and neuroinflammation. IL-1β causes neuronal activation in the brain and subsequent fatigue. In addition to proinflammatory molecules, potential partners in the complex brain signaling of fatigue include downregulatory mechanisms for inflammation and cellular stress responses and the neuropeptide hypocretin-1. These mechanisms all become constantly activated in chronic conditions. Genetic studies indicate that fatigue may have evolved to enhance survival during infection and injury.
Fatigue is a major clinical problem. Finding the right treatment is challenging, as no specific options exist and only a few of the mechanisms contributing to fatigue are known. Because fatigue is generated in the brain, further studies should focus on proteomics and specific candidate proteins in cerebrospinal fluid. Studies on genetic variants, gene activation, and epigenetics are also required.
慢性疲劳在癌症、神经退行性和慢性炎症性疾病中很常见，许多患者认为这是他们最糟糕的问题。最近，疲劳被越来越多地认为具有遗传和分子基础。
从生物学角度来看，疲劳是疾病行为反应的一部分，这是一种由先天免疫和神经炎症激活引发的复杂而自动的行为。IL-1β 在大脑中引起神经元激活，进而导致疲劳。除了促炎分子，疲劳复杂的大脑信号转导中的潜在伙伴还包括炎症和细胞应激反应的下调机制以及神经肽食欲素-1。这些机制在慢性疾病中都会持续激活。遗传研究表明，疲劳可能是为了在感染和损伤期间增强生存而进化的。
疲劳是一个主要的临床问题。找到合适的治疗方法具有挑战性，因为目前没有特定的选择，而且只有少数导致疲劳的机制被了解。由于疲劳是在大脑中产生的，因此进一步的研究应该集中在脑脊液中的蛋白质组学和特定候选蛋白上。还需要研究遗传变异、基因激活和表观遗传学。
