Anisman Hymie, Merali Zul
Institute of Neurosciences, Carleton University and Institute of Mental Health Research, Royal Ottawa Hospital, University of Ottawa, Canada.
Ann Med. 2003;35(1):2-11. doi: 10.1080/07853890310004075.
Cytokines, signaling molecules of the immune system, have been implicated as a contributing factor for mood disorders such as depression. Several lines of evidence supporting this contention are briefly reviewed and caveats are introduced. Essentially, a relationship between cytokines and depression is based on the findings that: 1) proinflammatory cytokines (interleukin-1, interleukin-6, tumor necrosis factor-alpha) and bacterial endotoxins elicit sickness behaviors (e.g., fatigue, soporific effects) and symptoms of anxiety/depression that may be attenuated by chronic antidepressant treatment, 2) cytokines induce neuroendocrine and central neurotransmitter changes reminiscent of those implicated in depression, and these effects are exacerbated by stressors, 3) severe depressive illness is accompanied by signs of immune activation and by elevations of cytokine production or levels, and 4) immunotherapy, using interleukin-2 or interferon-alpha, promotes depressive symptoms that are attenuated by antidepressant treatment. It is argued that cytokine synthesis and release, elicited upon activation of the inflammatory response system, provoke neuroendocrine and brain neurotransmitter changes that are interpreted by the brain as being stressors, and contribute to the development of depression. Furthermore, such effects are subject to a sensitization effect so that a history of stressful experiences or cytokine activation augment the response to later challenges and hence the evolution of depression
细胞因子作为免疫系统的信号分子，被认为是导致抑郁症等情绪障碍的一个因素。本文简要回顾了支持这一观点的几条证据，并介绍了一些注意事项。从本质上讲，细胞因子与抑郁症之间的关系基于以下发现：1）促炎细胞因子（白细胞介素-1、白细胞介素-6、肿瘤坏死因子-α）和细菌内毒素会引发疾病行为（如疲劳、嗜睡效应）以及焦虑/抑郁症状，而慢性抗抑郁治疗可能会减轻这些症状；2）细胞因子会引起神经内分泌和中枢神经递质的变化，这些变化与抑郁症中涉及的变化相似，并且应激源会加剧这些影响；3）严重的抑郁症伴有免疫激活的迹象以及细胞因子产生或水平的升高；4）使用白细胞介素-2或干扰素-α进行免疫治疗会引发抑郁症状，而抗抑郁治疗可以减轻这些症状。有人认为，炎症反应系统激活后引发的细胞因子合成和释放会引起神经内分泌和大脑神经递质的变化，大脑将这些变化解读为应激源，并导致抑郁症的发展。此外，这种影响会产生致敏作用，因此有压力经历或细胞因子激活的历史会增强对后续挑战的反应，从而促进抑郁症的发展。
