Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?

• Main Authors: Anna Clara Aragão Matos CARLOS (Author), José Vitor Mota LEMOS (Author), Marcela Maria Fontes BORGES (Author), Maria Carolina Portela ALBUQUERQUE (Author), Fabrício Bitu SOUSA (Author), Ana Paula Negreiros Nunes ALVES (Author), Thinali Sousa DANTAS (Author), Paulo Goberlânio de Barros SILVA (Author)
• Format: Book
• Published: University of São Paulo, 2023-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1678-7765; 10.1590/1678-7757-2023-0230
• Keywords: Zoledronic acid; Dental pulp; Acute-phase reaction; Inflammation; Dentistry; RK1-715
• Source: Journal of Applied Oral Science, Vol 31 (2023)

Abstract Objective To evaluate the influence of RORγT inhibition by digoxin on inflammatory changes related to interleukin-17 (IL-17) in the pulp of rats treated with zoledronate (ZOL). Methodology Forty male Wistar rats were divided into a negative control group (NCG) treated with saline solution, a positive control group (PCG) treated with ZOL (0.20 mg/kg), and three groups treated with ZOL and co-treated with digoxin 1, 2, or 4 mg/kg (DG1, 2, and 4). After four intravenous administrations of ZOL or saline solution in a 70-day protocol, the right molars were evaluated by histomorphometry (number of blood vessels, blood vessels/µm2, cells/µm2, total blood vessel area, and average blood vessel area) and immunohistochemistry (IL-17, TNF-α, IL-6, and TGF-β). The Kruskal-Wallis/Dunn test was used for statistical analysis. Results PCG showed an increase in total blood vessel area (p=0.008) and average blood vessel area (p=0.014), and digoxin treatment reversed these changes. DG4 showed a reduction in blood vessels/µm2 (p<0.001). In PCG odontoblasts, there was an increase in IL-17 (p=0.002) and TNF-α (p=0.002) immunostaining, and in DG4, these changes were reversed. Odontoblasts in the digoxin-treated groups also showed an increase in IL-6 immunostaining (p<0.001) and a reduction in TGF-β immunostaining (p=0.002), and all ZOL-treated groups showed an increase in IL-17 (p=0.011) and TNF-α (p=0.017) in non-odontoblasts cells. Conclusion ZOL induces TNF-α- and IL-17-dependent vasodilation and ectasia, and the classical Th17 response activation pathway does not seem to participate in this process.