Tocilizumab是一种人源化单克隆抗体，通过特异性结合白细胞介素-6（IL-6）的膜结合型受体（mIL-6R）与可溶性受体（sIL-6R），阻断IL-6与其受体IL-6R的相互作用，从而抑制下游JAK-STAT、MAPK/NF-κB等信号通路的激活[1]。该机制可有效干扰IL-6介导的炎症级联反应。Tocilizumab在人原代软骨细胞体外实验中能显著降低SOX-9、HIF-1α、BMP-2蛋白表达（分别下降71%、55%、81%）及IL-1β水平（下降67%），同时细胞活力仅轻微降低（27.7%），且未见明显细胞膜或核形态损伤，提示其具有较低细胞毒性[2]。

Tocilizumab在三阴性乳腺癌细胞模型中，通过抑制IL-6/STAT3/NF-κB正反馈环，能抑制细胞的增殖、迁移侵袭和上皮-间质转化过程，并下调Wnt/β-catenin通路以抑制肿瘤干细胞特性；同时可增强顺铂（Cisplatin，CDDP， 顺铂）的细胞毒性作用，并在人源化原位乳腺肿瘤小鼠模型中显著抑制肿瘤生长与EMT进程[3]。值得注意的是，体外实验证实Tocilizumab（RG-1569）能有效抑制人源细胞IL-6信号传导，但因种属特异性，无法与小鼠或大鼠IL-6受体结合，故在啮齿类细胞中无阻断效应[4]。

目前在动物实验层面，食蟹猴被选为Tocilizumab（托珠单抗）相关研究中最常用的物种，因为该抗体在体外和体内均能与猴IL-6R发生交叉反应。在食蟹猴胶原诱导性关节炎模型中，Tocilizumab给药后能显著减轻食蟹猴关节局部和全身的炎症反应，抑制炎症驱动的破骨细胞分化并使骨稳态恢复正常[5]。此外在猪崽（幼猪）缺血性骨坏死模型中使用15–20 mg/kg的Tocilizumab（每两周静脉注射），有效降低了滑膜炎程度、减少滑膜巨噬细胞的数量、抑制破骨细胞活性并促进新骨形成[6]。

参考文献及鸣谢

[1] Choong, D. J.; Tan, E. Does tocilizumab have a role in dermatology? A review of clinical applications, its adverse side effects and practical considerations. Dermatologic therapy 2021, 34 (4), e14990.

[2] Kilinc, B. R.; Kostak, F.; Yilmaz, O. F.; et al. The Effects of Tocilizumab on Inflammatory and Differentiation Pathways in Primary Human Chondrocytes: A Bioinformatic and In Vitro Approaches. International journal of rheumatic diseases 2025, 28 (7), e70336.

[3] Alraouji, N. N.; Al-Mohanna, F. H.; Ghebeh, H.; et al. Tocilizumab potentiates cisplatin cytotoxicity and targets cancer stem cells in triple-negative breast cancer. Molecular carcinogenesis 2020, 59 (9), 1041-1051.

[4] Lokau, J.; Kleinegger, F.; Garbers, Y.; et al. Tocilizumab does not block interleukin-6 (IL-6) signaling in murine cells. PloS one 2020, 15 (5), e0232612.

[5] Sheppard, M.; Laskou, F.; Stapleton, P. P.; et al. Tocilizumab (Actemra). Human vaccines & immunotherapeutics 2017, 13 (9), 1972-1988.

[6] Ren, Y.; Deng, Z.; Gokani, V.; et al. Anti-Interleukin-6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2021, 36 (2), 357-368.