Systemic lupus erythematosus (SLE) is an autoimmune disease associated with dysregulated interleukin (IL)-6 and autophagy. Although such disturbances are increasingly recognized in patients with SLE and animal models of the disease, little is known about the specific role of IL-6 and autophagy in SLE macrophages. Here, we investigated alterations in the IL-6 axis and autophagy in macrophages derived from patients with SLE and determined whether IL-6 modulates autophagy using human macrophage models. Serum IL-6 detected by ELISA was higher in SLE patients (n = 19) than in normal controls (n = 19, p < 0.001). Levels of the IL-6 receptor (IL-6R) and autophagic markers LC3B and p62 in SLE and normal macrophages were assessed by real-time PCR, western blotting, and immunofluorescence. Compared with normal macrophages, SLE macrophages not only overexpressed IL-6Rs but also exhibited impaired autophagic degradation as evidenced by elevated levels of LC3B and p62. In vitro analyses using macrophage models revealed that prolonged exposure to exogenous recombinant human IL-6 induced a marked impairment of autophagic degradation indicated by elevated levels of LC3B and p62 in both primary macrophages and transformed macrophages. Pretreatment with tocilizumab, a humanized anti-IL-6R monoclonal antibody, restored autophagic degradation and reversed p62 accumulation in a paracrine manner in macrophages. These findings demonstrate that SLE involves IL-6-induced impairment of autophagic degradation through augmentation of IL-6R in human macrophages.

系统性红斑狼疮（SLE）是与白介素（IL）-6失调和自噬相关的自身免疫性疾病。尽管在患有SLE和该疾病的动物模型的患者中越来越多地认识到这种障碍，但对IL-6和自噬在SLE巨噬细胞中的特定作用知之甚少。在这里，我们调查了SLE患者巨噬细胞中IL-6轴和自噬的变化，并使用人类巨噬细胞模型确定IL-6是否调节自噬。ELISA检测的血清IL-6在SLE患者中（n = 19）高于正常对照组（n = 19，p <0.001）。通过实时PCR，蛋白质印迹和免疫荧光评估SLE和正常巨噬细胞中IL-6受体（IL-6R）和自噬标记物LC3B和p62的水平。与正常的巨噬细胞相比，SLE巨噬细胞不仅过表达IL-6R，而且还表现出自噬降解受损，如LC3B和p62水平升高所证明的。体外使用巨噬细胞模型进行的分析表明，长时间暴露于外源重组人IL-6会导致自噬降解显着受损，这主要是由于巨噬细胞和转化巨噬细胞中LC3B和p62的水平升高所致。人源化抗IL-6R单克隆抗体tocilizumab的预处理可以在巨噬细胞中以旁分泌的方式恢复自噬降解并逆转p62的积累。这些发现表明，SLE通过增加人类巨噬细胞中的IL-6R而导致IL-6诱导的自噬降解受损。