Division of Rheumatology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Sci Rep. 2019 Nov 29;9(1):18000. doi: 10.1038/s41598-019-54549-5.
To prevent spinal progression in ankylosing spondylitis, initiating TNF-inhibitor treatment as early as possible is suggested. However, the outcomes are inconsistent in previous clinical studies. Here, we investigated the effect of TNF inhibition alone on spinal progression when used during arthritis development in a murine model. We injected 8-week-old SKG mice with curdlan (curdlan group). We injected adalimumab at 3 and 9 weeks after the first curdlan injection (ADA group). The clinical scores of peripheral arthritis decreased in the ADA group at 3 weeks after first adalimumab injection. Using positron emission tomography-magnetic resonance imaging and histologic examination, spinal inflammation was observed in the curdlan group, and was significantly deceased in the ADA group. However, spinal osteoblast activities by imaging using OsteoSense 680 EX and bone metabolism-related cytokines such as receptor activator of nuclear factor-kappa B ligand, osteoprotegerin, Dickkopf-1, and sclerostin levels except IL-17A level were not different between the two groups. We conclude that treating TNF inhibitor alone reduced peripheral arthritis score and spinal inflammation in curdlan-injected SKG mice but did not decrease the spinal osteoblast activity, suggesting little effect on spinal ankylosis.
为了预防强直性脊柱炎的脊柱进展,建议尽早开始使用 TNF 抑制剂治疗。然而,之前的临床研究结果并不一致。在这里,我们研究了在关节炎发展过程中使用 TNF 抑制剂单药治疗对小鼠模型脊柱进展的影响。我们给 8 周龄的 SKG 小鼠注射琼脂糖聚糖(琼脂糖聚糖组)。我们在第一次琼脂糖聚糖注射后 3 周和 9 周时注射阿达木单抗(ADA 组)。第一次阿达木单抗注射后 3 周,ADA 组的外周关节炎临床评分降低。通过正电子发射断层扫描-磁共振成像和组织学检查观察到琼脂糖聚糖组的脊柱炎症,ADA 组的脊柱炎症明显减少。然而,使用 OsteoSense 680 EX 进行的成像显示脊柱成骨细胞活性以及核因子-κB 配体受体激活剂、骨保护素、Dickkopf-1 和硬化素等骨代谢相关细胞因子的水平(除了 IL-17A 水平)在两组之间没有差异。我们得出结论,单独使用 TNF 抑制剂治疗可降低琼脂糖聚糖注射 SKG 小鼠的外周关节炎评分和脊柱炎症,但不能降低脊柱成骨细胞活性,表明对脊柱强直的影响较小。