Bösche Katharina, Weissenborn Karin, Christians Uwe, Witzke Oliver, Engler Harald, Schedlowski Manfred, Hadamitzky Martin
Institute of Medical Psychology and Behavioral Immunobiology, University Hospital, Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Department of Neurology, Hannover Medical School, 30625 Hannover, Germany.
Neuropharmacology. 2015 Sep;96(Pt A):83-93. doi: 10.1016/j.neuropharm.2014.12.008. Epub 2014 Dec 19.
60 years after the first successful kidney transplantation in humans, transplant patients have decent survival rates owing to a broad spectrum of immunosuppressive medication available today. Not only transplant patients, but also patients with inflammatory autoimmune diseases or cancer benefit from these life-saving immunosuppressive and anti-proliferative medications. However, this success is gained with the disadvantage of neuropsychological disturbances and mental health problems such as depression, anxiety and impaired quality of life after long-term treatment with immunosuppressive drugs. So far, surprisingly little is known about unwanted neuropsychological side effects of immunosuppressants and anti-proliferative drugs from the group of so called small molecule-drugs. This is partly due to the fact that it is difficult to disentangle whether and to what extent the observed neuropsychiatric disturbances are a direct result of the patient's medical history or of the immunosuppressive treatment. Thus, here we summarize experimental as well as clinical data of mammalian and human studies, with the focus on selected small-molecule drugs that are frequently employed in solid organ transplantation, autoimmune disorders or cancer therapy and their effects on neuropsychological functions, mood, and behavior. These data reveal the necessity to develop immunosuppressive and anti-proliferative drugs inducing fewer or no unwanted neuropsychological side effects, thereby increasing the quality of life in patients requiring long term immunosuppressive treatment. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'.
在人类首次成功进行肾脏移植60年后，由于如今有多种免疫抑制药物可供使用，移植患者有了不错的生存率。不仅移植患者，患有炎性自身免疫性疾病或癌症的患者也受益于这些挽救生命的免疫抑制和抗增殖药物。然而，这种成功是以神经心理障碍和心理健康问题为代价的，比如长期使用免疫抑制药物治疗后出现的抑郁、焦虑以及生活质量受损。到目前为止，对于所谓小分子药物类别的免疫抑制剂和抗增殖药物产生的不良神经心理副作用，人们了解得惊人地少。部分原因在于，很难厘清观察到的神经精神障碍究竟在多大程度上是患者病史的直接结果，还是免疫抑制治疗的直接结果。因此，在此我们总结哺乳动物和人类研究的实验及临床数据，重点关注实体器官移植、自身免疫性疾病或癌症治疗中常用的某些小分子药物及其对神经心理功能、情绪和行为的影响。这些数据表明，有必要研发产生较少或无不良神经心理副作用的免疫抑制和抗增殖药物，从而提高需要长期免疫抑制治疗的患者的生活质量。本文是名为“神经免疫学与突触功能”的特刊的一部分。
