CCL2’S IMMUNOMODULATORY ROLE IN THE TREATMENT OF PERIODONTAL DISEASE IN A CANINE MODEL

Periodontitis is an inflammatory disease of the oral cavity induced by bacterial biofilm in a susceptible host. It remains the leading cause of tooth loss in adults worldwide, affecting more than 46% of the adult population in the United States (Eke et al., 2015). Traditionally, this chronic inflammatory disease is treated through non-surgical and surgical therapy, aimed at mechanical debridement of teeth and reduction of bacterial biofilm. Although these methods have proven to be successful in reducing inflammation and disease progression, they are costly, time consuming and painful for patients to tolerate. In recent years, the focus has shifted towards therapies involving host modulation as an adjunct to non-surgical and surgical treatment. The purpose of this investigation was to evaluate the effects of the C-C motif chemokine ligand 2 (CCL2) on host immunomodulation in a canine ligature induced periodontitis model. Six female beagle dogs were used for the study. The subjects were randomly assigned to one of four treatment groups: healthy control, ligature induced periodontitis—untreated, ligature induced periodontitis treated with blank microparticles (MPs), and ligature induced periodontitis treated with recombinant human (rh) CCL2 MPs. The ligatures were secured to the subjects’ mandibular left and right first molar (M1) and fourth premolar (P4). Controlled release blank MPs or rhCCL2 containing MPs were injected into the marginal gingiva of the subjects at baseline (week 0), week 4, and week 8. Clinical parameters of probing depths and bleeding on probing (BOP) were assessed at baseline, 4 weeks, 8 weeks and 12 weeks. The dogs were sacrificed at week 12 and mandibular biopsies were harvested for micro-computed topography (CT) analysis. The administration of rhCCL2 MPs, even in the presence of chronic inflammation, provided protection against attachment loss as measured by changes in probing depth and alveolar bone loss compared to the untreated groups. We can conclude from this study that rhCCL2 MPs successfully modulated the immune response to periodontal pathogens in the ligature induced periodontitis canine model, resulting in attachment levels comparable to the healthy control group