IL-17 Receptor inhibition with brodalumab limits experimental periodontitis

Area of Science:

• Immunology
• Periodontology
• Pharmacology

Background:

• Periodontal disease (PD) is a chronic inflammatory condition characterized by connective tissue and alveolar bone loss.
• Dysregulated host immunity significantly contributes to PD pathogenesis.
• The IL-17 pathway is implicated in periodontal inflammation and treatment response, making it a potential therapeutic target.

Purpose of the Study:

• To investigate the therapeutic potential of IL-17 receptor (IL-17R) blockade in experimental periodontitis.
• To evaluate the efficacy of brodalumab, an IL-17R inhibitor, in modulating inflammatory responses and protecting against alveolar bone loss.

Main Methods:

• Human gingival and salivary samples were analyzed for immune profiles and inflammatory markers.
• Mice with ligature-induced periodontitis (LIP) received local gingival injections of brodalumab.
• Gingival inflammation was quantified using qPCR and flow cytometry; alveolar bone loss was assessed via micro-CT.

Main Results:

• Elevated IL-17 expression in PD patients decreased after therapy, correlating with reduced inflammation.
• Brodumab treatment in LIP mice suppressed IL-17A and IL-17B, reduced neutrophil infiltration, and promoted M2-like macrophage skewing.
• Brodumab administration dose-dependently reduced alveolar bone loss and preserved bone quality, increasing bone volume and mineral density.

Conclusions:

• Local IL-17R blockade with brodalumab attenuates IL-17-driven inflammation and protects against bone loss in experimental periodontitis.
• IL-17R blockade is a potential host-modulatory strategy for periodontal disease.
• This approach could complement conventional periodontal therapy to mitigate tissue destruction.