Scholarlink

Background <p>Periodontal disease (PD) is a chronic, biofilm-driven inflammatory condition in which connective tissue destruction and alveolar bone loss are driven largely by dysregulated host immunity. Prior experimental and clinical studies have linked IL-17 pathway activity to periodontal inflammation and treatment response, supporting its relevance as a therapeutic target in PD. Rather than targeting individual IL-17 isoforms, IL-17R blockade offers an alternative strategy because it serves as a shared downstream signaling node for multiple IL-17 family cytokines, potentially enabling broader modulation of inflammatory signaling. However, the therapeutic potential of IL-17R blockade in PD remains largely unexplored.</p> Methods <p>Gingival and salivary immune profiles and inflammatory markers were assessed in periodontally healthy, diseased, and post-therapy subjects. For mechanistic studies, mice subjected to ligature-induced periodontitis (LIP) received local gingival injection of the IL-17 receptor inhibitor brodalumab at 5 or 20&#xa0;mg/kg, or vehicle control every 48 h. Animals were euthanized on day 4 or day 8 post-treatment, and gingival inflammatory responses were quantified by qPCR and flow cytometry. Alveolar bone outcomes were assessed by micro-CT, including CEJ–ABC distance as a measure of bone loss, and bone volume and bone mineral density as measures of bone quality.</p> Results <p>Gingival and salivary CD4⁺IL-17⁺ T cells were increased in PD and were markedly reduced after therapy, supporting the association of IL-17-driven immune responses with disease activity and their resolution following treatment. This observation was validated in human gingival biopsies, where IL-17 expression was elevated in PD and markedly reduced after nonsurgical periodontal therapy, accompanied by lower inflammatory cytokine expression and a shift toward a healthy control profile. In LIP mice, local injection of brodalumab reduced gingival inflammatory transcripts, with IL-17A suppressed by day 4 and sustained through day 8, alongside reduced IL-17B, indicating broader dampening of IL-17 signaling. These changes were associated with reduced gingival neutrophil infiltration and M2-like macrophage skewing, indicating that brodalumab promotes the resolution of inflammation. Micro-CT demonstrated lower alveolar bone loss in a dose-dependent manner in brodalumab treated animals. Brodalumab also preserved bone quality, increasing bone volume and bone mineral density, most prominently at the higher dose, which approached no-ligature values by day 8.</p> Conclusion <p>Local gingival administration of brodalumab attenuates IL-17–associated inflammatory responses and protects against alveolar bone loss in experimental periodontitis. Our findings support IL-17R blockade as a promising host-modulatory strategy that could serve as an adjunct to conventional periodontal care to limit periodontal tissue destruction.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

IL-17 Receptor inhibition with brodalumab limits experimental periodontitis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月29日

查看全文
  • Araceli Valverde,
  • Raza Ali Naqvi,
  • Matt Tokarski,
  • Kristofer Ceredon,
  • Joseph Gluck,
  • Sarah Elshourbagy,
  • Gloria Martínez,
  • Maria Brambilla,
  • Salvador Nares,
  • Joel Schwartz,
  • Afsar R. Naqvi

摘要

Background

Periodontal disease (PD) is a chronic, biofilm-driven inflammatory condition in which connective tissue destruction and alveolar bone loss are driven largely by dysregulated host immunity. Prior experimental and clinical studies have linked IL-17 pathway activity to periodontal inflammation and treatment response, supporting its relevance as a therapeutic target in PD. Rather than targeting individual IL-17 isoforms, IL-17R blockade offers an alternative strategy because it serves as a shared downstream signaling node for multiple IL-17 family cytokines, potentially enabling broader modulation of inflammatory signaling. However, the therapeutic potential of IL-17R blockade in PD remains largely unexplored.

Methods

Gingival and salivary immune profiles and inflammatory markers were assessed in periodontally healthy, diseased, and post-therapy subjects. For mechanistic studies, mice subjected to ligature-induced periodontitis (LIP) received local gingival injection of the IL-17 receptor inhibitor brodalumab at 5 or 20 mg/kg, or vehicle control every 48 h. Animals were euthanized on day 4 or day 8 post-treatment, and gingival inflammatory responses were quantified by qPCR and flow cytometry. Alveolar bone outcomes were assessed by micro-CT, including CEJ–ABC distance as a measure of bone loss, and bone volume and bone mineral density as measures of bone quality.

Results

Gingival and salivary CD4⁺IL-17⁺ T cells were increased in PD and were markedly reduced after therapy, supporting the association of IL-17-driven immune responses with disease activity and their resolution following treatment. This observation was validated in human gingival biopsies, where IL-17 expression was elevated in PD and markedly reduced after nonsurgical periodontal therapy, accompanied by lower inflammatory cytokine expression and a shift toward a healthy control profile. In LIP mice, local injection of brodalumab reduced gingival inflammatory transcripts, with IL-17A suppressed by day 4 and sustained through day 8, alongside reduced IL-17B, indicating broader dampening of IL-17 signaling. These changes were associated with reduced gingival neutrophil infiltration and M2-like macrophage skewing, indicating that brodalumab promotes the resolution of inflammation. Micro-CT demonstrated lower alveolar bone loss in a dose-dependent manner in brodalumab treated animals. Brodalumab also preserved bone quality, increasing bone volume and bone mineral density, most prominently at the higher dose, which approached no-ligature values by day 8.

Conclusion

Local gingival administration of brodalumab attenuates IL-17–associated inflammatory responses and protects against alveolar bone loss in experimental periodontitis. Our findings support IL-17R blockade as a promising host-modulatory strategy that could serve as an adjunct to conventional periodontal care to limit periodontal tissue destruction.