Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Pathology, Cleveland Clinic, Cleveland, OH, USA.
Lupus. 2019 Nov;28(13):1510-1523. doi: 10.1177/0961203319872265. Epub 2019 Aug 31.
Many systemic lupus erythematosus patients display a type I interferon (IFN) signature, and IFNα levels positively correlate with disease severity. Previous studies blocking the type I IFN pathway systemically in lupus models showed some beneficial effects. However, its effects on neuropsychiatric manifestations have yet to be carefully assessed, even though IFNα has been associated with induction of depression. Our aim was to investigate whether disrupting the type I IFN pathway would attenuate the development of murine neuropsychiatric lupus.
Female MRL/ mice were administered an antitype I IFN receptor (IFNAR) antibody or a control antibody intraperitoneally three times weekly for 12 weeks starting at age 4-5 weeks. Behavior was assessed during and at the end of the treatment schedule.
No significant differences were seen between the anti-IFNAR- and control-treated mice when assessing for depression-like behavior or cognitive dysfunction, although anti-IFNAR antibody-treated mice displayed significant decreases in levels of IFN-stimulated genes. Anti-IFNAR treatment also did not significantly improve brain histology, cellular infiltration, or blood-brain barrier integrity.
Surprisingly, our results showed no improvement in neuropsychiatric disease and suggest that the role of IFNAR signaling in the pathogenesis of neuropsychiatric lupus continues to need to be carefully assessed.
许多红斑狼疮患者表现出 I 型干扰素（IFN）特征，IFNα 水平与疾病严重程度呈正相关。既往研究表明，在狼疮模型中全身性阻断 I 型 IFN 通路具有一定的有益效果。然而，其对神经精神表现的影响尚未得到仔细评估，尽管 IFNα 与抑郁症的发生有关。我们的目的是研究阻断 I 型 IFN 通路是否会减轻小鼠神经精神性狼疮的发生。
4-5 周龄雌性 MRL/狼疮小鼠每周腹腔内注射抗 I 型 IFN 受体（IFNAR）抗体或对照抗体 3 次，共 12 周。在治疗期间和结束时评估行为。
在评估抑郁样行为或认知功能障碍时，抗 IFNAR 抗体治疗组和对照组小鼠之间未见显著差异，尽管抗 IFNAR 抗体治疗组 IFN 刺激基因水平显著降低。抗 IFNAR 治疗也未显著改善脑组织病理学、细胞浸润或血脑屏障完整性。
令人惊讶的是，我们的结果显示神经精神疾病无改善，表明 IFNAR 信号通路在神经精神性狼疮发病机制中的作用仍需仔细评估。
