Therapeutic Effects of Tofacitinib on Pristane-Induced Murine Lupus

Objectives: This study aims to investigate the effectiveness of tofacitinib, a Janus kinase (JAK) 1/JAK3 inhibitor, in treating murine lupus, and also explore 12 related genes downstream of JAK-signal transducer and activator of transcription (STAT) signaling pathways to find the underlying mechanism.

Materials and methods: This study was conducted between July 2017 and January 2020. Fifty-seven female BALB/c mice (aging 8 to 10 weeks old; weighing 18 to 20 g) were assigned to a saline control (SC) group and a pristane-induced lupus group. The latter included four groups, namely, pristane control (PC), tofacitinib (T), methylprednisolone (MP), and tofacitinib plus methylprednisolone (T+MP). Animal models of lupus were induced with pristane, whereas SC mice were treated with normal saline. From the 22^nd week after induction, each group was given the aforementioned corresponding intervention for 11 weeks. The following variables were tested: serum concentrations of anti-double-stranded deoxyribonucleic acid (anti-dsDNA), interleukin 6 (IL-6), and interferon gamma (IFN-γ); number of regulatory T (Treg) cells; messenger ribonucleic acid levels of forkhead box P3 and 12 related genes downstream of JAK-STAT pathway; and renal impairment.

Results: Red swollen joints and proteinuria were first observed in PC after the 12^th week. After treatment, T, MP, and T+MP showed relieved red swollen joints and splenomegaly, as well as decreased urine protein, anti-dsDNA, IL-6, IFN-γ, Treg cells, pathological scores, and hyperplasia of mesangial matrix in glomeruli compared with PC. The IFN regulatory factor 7 level was higher in T+MP (p0.05) and MP (p>0.05) than in PC after treatment. The expression of suppressor of cytokine signaling (SOCS) 1 was lower in T (p>0.05), T+MP (p0.05) than in PC. The SOCS3 level was higher in T (p>0.05) and T+MP (p0.05) than in PC.

Conclusion: Tofacitinib can ameliorate glomerulonephritis and arthritis in a pristane-induced murine model of lupus. SOCS3 gene may be involved in the therapeutic mechanism of tofacitinib.