Ur E, White P D, Grossman A
Department of Endocrinology, St. Bartholomew's Hospital, London, England.
Eur Arch Psychiatry Clin Neurosci. 1992;241(5):317-22. doi: 10.1007/BF02195983.
Abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis are a well recognised feature of endogenous depression. The mechanism underlying this phenomenon remains obscure although there is strong evidence suggesting excessive CRH activity at the level of the hypothalamus. We propose a novel hypothesis in which we suggest that the aetiological antecent to CRH hyperactivity is cytokine activation in the brain. It is now well established both that interleukins -1 and -6 are produced in a number of central loci and that cytokines are potent stimulators of the HPA axis. Hence, we suggest that activation of IL-1 and IL-6 by specific mechanisms (such as neurotropic viral infection) in combination with the consequent CRH-41 stimulation, may (via their known biological effects) underly many of the features found in major depression and other related disorders, particularly where chronic fatigue is a prominent part of the symptom complex. This theory has considerable heuristic value and suggests a number of experimental stratagems which may employed in order to confirm or reject it.
下丘脑 - 垂体 - 肾上腺（HPA）轴调节异常是内源性抑郁症公认的一个特征。尽管有强有力的证据表明下丘脑水平存在促肾上腺皮质激素释放激素（CRH）活性过高，但这一现象背后的机制仍不清楚。我们提出了一个新的假说，认为CRH活性亢进的病因学先兆是大脑中的细胞因子激活。现在已经明确，白细胞介素 -1和 -6在多个中枢位点产生，并且细胞因子是HPA轴的强效刺激物。因此，我们认为通过特定机制（如嗜神经性病毒感染）激活IL -1和IL -6，并随之产生CRH -41刺激，可能（通过其已知的生物学效应）构成重度抑郁症和其他相关疾病中许多特征的基础，特别是在慢性疲劳是症状复合体的突出部分的情况下。这一理论具有相当大的启发价值，并提出了一些可用于证实或反驳它的实验策略。
