Specific inhibition of IL‐6 receptor attenuates inflammatory bone loss in experimental periodontitis

牙槽 牙周炎 促炎细胞因子 兰克尔 医学 骨保护素 炎症 吸收 发病机制 骨吸收 内科学 破骨细胞 受体 免疫学 内分泌学 牙科 激活剂(遗传学)
作者
Gustavo Henrique Apolinário Vieira,Ana Rivas,Karine Costa,Luis Fernando Ferreira Oliveira,Kleber Tanaka Suzuki,Michel Reis Messora,Milla Sprone Tavares Ricoldi,Adriana Luisa Gonçalves Almeida,Mário Taba
出处
期刊:Journal of Periodontology [Wiley]
卷期号:92 (10): 1460-1469 被引量:48
标识
DOI:10.1002/jper.20-0455
摘要

Abstract Background Periodontal pathogenesis takes into consideration that disease results from a complex inflammatory immune response. Among the major cytokines related to periodontal damage, interleukin (IL)‐6 enhances a cascade of tissue destruction. Tocilizumab (TCZ) is a humanized monoclonal anti‐human IL‐6 receptor that inhibits IL‐6‒mediated proinflammatory activity. This study aimed to elucidate whether TCZ inhibits the deleterious effect of ligature‐induced periodontitis. Methods Experimental ligature‐induced periodontitis was treated with systemic administration of TCZ intraperitoneally in three different concentration dosages (2 mg/kg, 4 mg/kg, and 8 mg/kg. Euthanasia occurred at 7 and 14 days after the initiation of the study. Local changes in the alveolar bone were measured by bone volume, the ratio of bone volume, and trabecular thickness using microcomputed tomography. Attachment loss and inflammatory infiltrate were evaluated by histology. Immune response was analyzed focusing on the Th17 pattern. Results TCZ inhibited alveolar bone resorption and attachment loss in 7 and 14 days for all dosage groups in comparison to controls ( P < 0.05). Besides, TCZ induced lower expression of inflammatory infiltrate ( P <0.05) and less production of Th17‐related cytokines ( P <0.05) and RANKL ( P <0.05). Conclusions The inhibition of IL‐6‒mediated proinflammatory activity by IL‐6R blocking reduced alveolar bone resorption and attachment loss supported by the modulation of the Th17 periodontal response. Considering the inflammatory status, modulatory therapy may be a promising approach to periodontal disease.
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