<p>To examine the impact of locally applied Tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, on experimental periodontitis. 50 Wistar male rats were divided into three groups: (1) Healthy (<i>n</i> = 10), (2) Experimental Periodontitis (<i>n</i> = 20), and (3) Experimental Periodontitis + TCZ (<i>n</i> = 20). The animals received an intrapapillary injection of TCZ (2&#xa0;mg/kg). After three days, periodontitis was induced by placing a ligature around the upper left 2nd molar for ten days. In euthanasia, blood, maxillae, and gingival samples were removed for biochemical, microtomography, histologic, immunohistochemistry, cytokine assay and RT-qPCR analyses. TCZ was able to attenuate linear alveolar bone loss (<i>p</i> &lt; 0.05) and the loss of the number of bone trabeculae (<i>p</i> &lt; 0.05), and to reduce the severity of inflammation (<i>p</i> &lt; 0.05). Its local administration decreased gingival tissue levels of IL-6 and TNF-α (<i>p</i> &lt; 0.05), the intensity of RANKL immunostaining (<i>p</i> &lt; 0.0001) and mRNA expression of SOD (<i>p</i> &lt; 0.001) and GPx (<i>p</i> &lt; 0.01). These findings suggest the anti-inflammatory efficacy of Tocilizumab administered in periodontitis. Cytokines play a major role in destroying periodontal support tissue during periodontitis. Inhibition of IL-6 receptor demonstrated to reduce periodontal inflammation and bone loss, and may be considered as an adjunctive approach in refractory or severe periodontitis cases that do not adequately respond to conventional therapy.</p>

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Effectiveness of local Tocilizumab administration in mitigating alveolar bone loss and inflammation in experimental periodontitis

  • Agnes Andrade Martins,
  • Maria Laura Souza Lima,
  • Gustavo Henrique Apolinário Vieira,
  • Heloísa Espínola Sena Costa,
  • Renata Ferreira Carvalho Leitão,
  • Susana Barbosa Ribeiro,
  • Caroline Addison Carvalho Xavier Medeiros,
  • Davi Neto Araújo Silva,
  • Rungsinee Suksakulchai,
  • Flavia Q. Pirih,
  • Gerly Anne Castro Brito,
  • Vinícius Barreto Garcia,
  • Raimundo Fernandes Araújo Júnior,
  • Ruthineia Diógenes Alves Uchôa Lins,
  • Aurigena Antunes Araújo

摘要

To examine the impact of locally applied Tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, on experimental periodontitis. 50 Wistar male rats were divided into three groups: (1) Healthy (n = 10), (2) Experimental Periodontitis (n = 20), and (3) Experimental Periodontitis + TCZ (n = 20). The animals received an intrapapillary injection of TCZ (2 mg/kg). After three days, periodontitis was induced by placing a ligature around the upper left 2nd molar for ten days. In euthanasia, blood, maxillae, and gingival samples were removed for biochemical, microtomography, histologic, immunohistochemistry, cytokine assay and RT-qPCR analyses. TCZ was able to attenuate linear alveolar bone loss (p < 0.05) and the loss of the number of bone trabeculae (p < 0.05), and to reduce the severity of inflammation (p < 0.05). Its local administration decreased gingival tissue levels of IL-6 and TNF-α (p < 0.05), the intensity of RANKL immunostaining (p < 0.0001) and mRNA expression of SOD (p < 0.001) and GPx (p < 0.01). These findings suggest the anti-inflammatory efficacy of Tocilizumab administered in periodontitis. Cytokines play a major role in destroying periodontal support tissue during periodontitis. Inhibition of IL-6 receptor demonstrated to reduce periodontal inflammation and bone loss, and may be considered as an adjunctive approach in refractory or severe periodontitis cases that do not adequately respond to conventional therapy.