Tocilizumab, a Potent Interleukin-6 Receptor Inhibitor, Decreases Bone Resorption and Increases the Rate of Bacterial Infection After Tooth Extraction in Rats

• Published in: Journal of oral and maxillofacial surgery Vol. 78; no. 12; pp. 2138 - 2146
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2020; American Association of Oral and Maxillofacial Surgeons
• Subjects: Alveolar Bone Loss; Animals; Antibodies, Monoclonal, Humanized; Bacterial Infections; Bone Resorption; Dentistry; Dentoalveolar Surgery; Male; Rats; Rats, Wistar; Receptors, Interleukin-6; Tooth Extraction - adverse effects
• ISSN: 0278-2391; 1531-5053
• DOI: 10.1016/j.joms.2020.08.012

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.