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

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

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...

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Published in:Journal of periodontology (1970) Vol. 92; no. 10; pp. 1460 - 1469
Main Authors: Apolinário Vieira, Gustavo H., Aparecida Rivas, Ana Carolina, Figueiredo Costa, Karine, Ferreira Oliveira, Luis Fernando, Tanaka Suzuki, Kleber, Reis Messora, Michel, Sprone Ricoldi, Milla, Gonçalves de Almeida, Adriana Luisa, Taba, Mario
Format: Journal Article
Language:English
Published: United States 01-10-2021
Subjects:
Alveolar Bone Loss - diagnostic imaging
Alveolar Bone Loss - drug therapy
Alveolar Bone Loss - prevention & control
Animals
anti‐inflammatory agents
cytokines
Disease Models, Animal
Interleukin-6
periodontitis
Periodontitis - drug therapy
pharmacology
Receptors, Interleukin-6
X-Ray Microtomography
anti-inflammatory agents
cytokines
periodontitis
pharmacology
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Summary: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.
Bibliography:Funding information
Scholarship from São Paulo State Foundation—FAPESP, Grant Number: 17/26137‐3 to DR. Apolinario Vieira and Prof TAba JR, and National Council For Scientific And Technological Development, Grant Number: 439497/2016‐7 to GHAV.
Ana C. A. Rivas and Gustavo H. Apolinário Vieira contributed equally to this article.
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ISSN:0022-3492
1943-3670
DOI:10.1002/JPER.20-0455