Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Military Institute of Hygiene and Epidemiology, Warsaw, Poland.
J Infect Dis. 2022 May 4;225(9):1545-1553. doi: 10.1093/infdis/jiac040.
Tofacitinib, a Janus kinase inhibitor, is a novel immunosuppressive drug for treatment of rheumatoid arthritis. Herpes simplex virus type 1 (HSV-1) may cause encephalitis during primary infection or following reactivation from a latent state. Long-term tofacitinib treatment may increase the risk of this life-threatening condition. The aim of this study was to investigate the effect of tofacitinib on HSV-1 primary infection using a mouse model. Mice pretreated with tofacitinib were intranasally infected with a clinical strain of HSV-1 and monitored for infection severity and antiviral response. Tofacitinib treatment of HSV-1 primary infection resulted in increased viral loads and worsened clinical outcome. Furthermore, tofacitinib promoted M2 anti-inflammatory phenotype of microglia and infiltrating monocytes, as well as inhibited production of inflammatory and antiviral cytokines by macrophages in vitro. Our findings show that treatment with tofacitinib increases severity of herpes simplex encephalitis in mice, by impairing antiviral response induced by monocytes and microglia.
托法替尼是一种 Janus 激酶抑制剂，是一种新型免疫抑制剂，用于治疗类风湿关节炎。单纯疱疹病毒 1 型（HSV-1）在原发感染或潜伏状态重新激活时可能导致脑炎。长期使用托法替尼可能会增加这种危及生命的疾病的风险。本研究旨在使用小鼠模型研究托法替尼对 HSV-1 原发感染的影响。用托法替尼预处理的小鼠经鼻腔感染临床株 HSV-1，并监测感染严重程度和抗病毒反应。托法替尼治疗 HSV-1 原发感染导致病毒载量增加和临床结局恶化。此外，托法替尼促进了小胶质细胞和浸润性单核细胞的 M2 抗炎表型，并抑制了体外巨噬细胞产生炎症和抗病毒细胞因子。我们的研究结果表明，托法替尼治疗通过损害单核细胞和小胶质细胞诱导的抗病毒反应，增加了小鼠单纯疱疹脑炎的严重程度。
