Imaculada de Queiroz Rodrigues Maria, Ohana de Lima Martins Joyce, Silva Paulo Goberlânio de Barros, Carlos Ferreira Júnior Antônio Ernando, Quezado Lima Verde Maria Elisa, Sousa Fabrício Bitú, Lima Mota Mário Rogério, Negreiros Nunes Alves Ana Paula
Master Student, Laboratory of Bucodental Pathology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Professor, Laboratory of Bucodental Pathology, Federal University of Ceará, Fortaleza, Ceará, Brazil; Professor, Unichristus, Department of Dentistry, Fortaleza, Ceará, Brazil.
J Oral Maxillofac Surg. 2020 Dec;78(12):2138-2146. doi: 10.1016/j.joms.2020.08.012. Epub 2020 Aug 15.
Our objective was to evaluate the influence of pretreatment with tocilizumab (TCZ) in bone healing after tooth extraction in rats.
Wistar male rats were equally divided into sham (ie, nonoperated), saline (both treated with 0.1 ml/kg saline), and six TCZ groups treated with 1, 2, 4, 8, 16, and 32 mg/kg TCZ (TCZ1 to TCZ32, respectively). Twenty-four hours after administration of vehicle or TCZ, exodontia of the first lower left molar was performed, and the animals were euthanized three days later for hematological analysis and organ (liver, spleen, and kidney mass indexes, and histological evaluation), gingiva (myeloperoxidase [MPO] assay), and mandible (radiographic, histomorphometric analysis, and IL-6 immunostaining) evaluation. Analysis of variance/Bonferroni test (statistical significance, P < .05) was performed using GraphPad Prism version 5.0 (GraphPad Inc, San Diego, CA, USA).
There was no difference in radiographic results; however, leukopenia (P = .039) and neutropenia (P < .001) were statistically significant in the TCZ16 and TCZ32 groups. Weight loss (P < .001) and reduced liver index (P = .001) were significantly dose-dependent; however, no histological alterations were observed in the other organs. Osteoclast counts were reduced in groups TCZ4 to TCZ32 (P < .001), and IL-6 immunostaining increased in the TCZ8 to TCZ32 groups (P < .001). Alveolar infection rates increased in groups TCZ4 to TCZ32 (P < .001), and MPO had a biphasic response, exhibiting a reduction in groups TCZ2 and TCZ4, and an increase in group TCZ32 (P = .004).
TCZ-induced immunosuppression led to a reduction in osteoclast function, an increase in alveolar infection, and compensatory neutrophil infiltration.
我们的目标是评估托珠单抗（TCZ）预处理对大鼠拔牙后骨愈合的影响。
将雄性Wistar大鼠平均分为假手术组（即未手术组）、生理盐水组（均用0.1 ml/kg生理盐水处理）以及六个分别用1、2、4、8、16和32 mg/kg TCZ处理的TCZ组（分别为TCZ1至TCZ32）。在给予赋形剂或TCZ 24小时后，拔除左下第一磨牙，三天后对动物实施安乐死以进行血液学分析和器官（肝脏、脾脏和肾脏质量指数以及组织学评估）、牙龈（髓过氧化物酶[MPO]检测）和下颌骨（影像学、组织形态计量学分析以及IL-6免疫染色）评估。使用GraphPad Prism 5.0版本（美国加利福尼亚州圣地亚哥的GraphPad公司）进行方差分析/邦费罗尼检验（统计学显著性，P <.05）。
影像学结果无差异；然而，TCZ16组和TCZ32组出现白细胞减少（P = 0.039）和中性粒细胞减少（P < 0.001），具有统计学显著性。体重减轻（P < 0.001）和肝脏指数降低（P = 0.001）呈显著剂量依赖性；然而，在其他器官未观察到组织学改变。TCZ4至TCZ32组破骨细胞计数减少（P < 0.001），TCZ8至TCZ32组IL-6免疫染色增加（P < 0.001）。TCZ4至TCZ32组牙槽感染率增加（P < 0.001），MPO呈现双相反应，在TCZ2组和TCZ4组降低，在TCZ32组增加（P = 0.004）。
TCZ诱导的免疫抑制导致破骨细胞功能降低、牙槽感染增加以及代偿性中性粒细胞浸润。
