Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ damage. Neuropsychiatric lupus (NPSLE) is one of the most common manifestations of human SLE, often causing depression. Interferon-α (IFNα) is a central mediator in disease pathogenesis. Administration of IFNα to patients with chronic viral infections or cancers causes depressive symptoms. Angiotensin-converting enzyme (ACE) is part of the kallikrein–kinin/renin-angiotensin (KKS/RAS) system that regulates many physiological processes, including inflammation, and brain functions. It is known that ACE degrades bradykinin (BK) into inactive peptides. We have previously shown in an in vitro model of mouse bone-marrow-derived dendritic cells (BMDC) and human peripheral blood mononuclear cells that captopril (a centrally acting ACE inhibitor-ACEi) suppressed Type I IFN responsive gene (IRG) expression. In this report, we used the MRL/lpr lupus-prone mouse model, an established model to study NPSLE, to determine the in vivo effects of captopril on Type I IFN and associated immune responses in the periphery and brain and effects on behavior. Administering captopril to MRL/lpr mice decreased expression of IRGs in brain, spleen and kidney, decreased circulating and tissue IFNα levels, decreased microglial activation (IBA-1 expression) and reduced depressive-like behavior. Serotonin levels that are decreased in depression were increased by captopril treatment. Captopril also reduced autoantibody levels in plasma and immune complex deposition in kidney and brain. Thus, ACEi’s may have potential for therapeutic use for systemic and NPSLE.

系统性红斑狼疮（SLE）是一种以多器官损害为特征的自身免疫性疾病。神经精神狼疮 (NPSLE) 是人类 SLE 最常见的表现之一，常常导致抑郁。干扰素-α (IFNα) 是疾病发病机制的核心介质。对患有慢性病毒感染或癌症的患者施用 IFNα 会导致抑郁症状。血管紧张素转换酶 (ACE) 是激肽释放酶-激肽/肾素-血管紧张素 (KKS/RAS) 系统的一部分，可调节许多生理过程，包括炎症和大脑功能。众所周知，ACE 可将缓激肽 (BK) 降解为无活性的肽。我们之前已经在一个体外在小鼠骨髓源性树突状细胞 (BMDC) 和人外周血单核细胞模型中，卡托普利（一种中枢作用的 ACE 抑制剂 -ACEi）抑制 I 型 IFN 反应基因 (IRG) 的表达。在本报告中，我们使用 MRL/lpr 狼疮倾向小鼠模型（一种用于研究 NPSLE 的既定模型）来确定体内卡托普利对 I 型干扰素以及外周和大脑相关免疫反应的影响以及对行为的影响。给 MRL/lpr 小鼠施用卡托普利可降低脑、脾和肾中 IRG 的表达，降低循环和组织 IFNα 水平​​，减少小胶质细胞激活（IBA-1 表达）并减少抑郁样行为。卡托普利治疗可增加抑郁症时降低的血清素水平。卡托普利还降低血浆中的自身抗体水平以及肾脏和大脑中免疫复合物的沉积。因此，ACEi 可能具有治疗全身性和 NPSLE 的潜力。