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 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.

Automated summary

The study showed that tocilizumab can reduce alveolar bone resorption and attachment loss caused by periodontitis by inhibiting IL-6-mediated proinflammatory activity. Additionally, it decreased inflammatory infiltrate and production of Th17-related cytokines, suggesting that modulatory therapy may be a promising approach for periodontal disease.