ABSTRACT
OBJECTIVES: To assess the influence of antiresorptive/antiangiogenic therapy on the spreading of peri-implant infections in the pharyngeal region. MATERIAL AND METHODS: This analysis was based on tissue biopsies obtained from a total of twenty-five albino rats having either received (1) amino-bisphosphonate (Zoledronate) (Zo) (n=4), (2) RANKL inhibitor (Denosumab) (De) (n=4), (3) antiangiogenic medication (Bevacizumab) (Be) (n=4), (4) Zo+Be (n=3), (5) De+Be (n=5), or (6) no medication (Co) (n=5). Drug administration was repeated at 12 weeks. Chronic-type peri-implant infections were induced at titanium implants located in the upper jaws. The surface area (%) of infiltrated connective tissue (ICT) and CD68-positive cells was assessed within the lateral pharyngeal/retropharyngeal connective tissue zone. RESULTS: Mean (±SD) and median ICT% values and CD68 counts were markedly highest in the De+Be (11.10±6.04; 11.81; 95% CI - 3.89; 26.11) and De (5.70±5.06; 6.19; 95% CI - 2.34; 13.75) groups, reaching statistical significance for De CD68 counts over the Co (0.18±0.25; 0.18; 95% CI -2.14; 2.51) group. In both De+Be and De groups, the ICTs were occasionally associated with an ulceration of the epithelial compartment. CONCLUSIONS: Induced peri-implant infections were not associated with any inflammatory lesions in pharyngeal tissues. While these findings were similar under Zo and Be medication, De and De+Be had a marked effect on ICT and CD68 values. The clinical relevance of these adverse findings needs further investigation.
Subject(s)
Bone Density Conservation Agents , Diphosphonates , Animals , Connective Tissue , Rats , TitaniumABSTRACT
BACKGROUND AND OBJECTIVE: Macrophages' cytokine expression and polarization play a substantial role in the host's "destructive" inflammatory response to periodontal and peri-implant pathogens. This study aimed to evaluate cell viability, anti-inflammatory activity, and macrophage polarization properties of different cranberry concentrates. METHODS: THP-1 cells (monocytic line) were treated with phorbol myristic acid to induce macrophage differentiation. Human gingival fibroblasts (HFIB-G cell line), osteosarcoma-derived osteoblasts (SAOS-2 cell line), and induced macrophages were treated with cranberry concentrates at 25, 50, and 100 µg/mL for 120 seconds, 1 hour and 24 hours. Untreated cells at the same time points served as controls. For anti-inflammatory analysis, induced macrophages exposed to cranberry concentrates (A-type PACs) were stimulated with lipopolysaccharides (LPS) derived from E coli for 24 hours. Cell viability, interleukin (IL)-8, IL-1 ß, IL-6, and IL-10 expression of LPS-stimulated macrophages, and macrophage polarization markers were evaluated through determination of live-cell protease activity, enzyme-linked immunosorbent assay, and immunofluorescence staining semi-quantification. RESULTS: Cranberry concentrates (A-type PACs) did not reduce HGF, SAOS-2, and macrophage viability after 24 hours of exposure. Pro-inflammatory cytokine expression (ie IL-8 and IL-6) was downregulated in LPS-stimulated macrophages by cranberry concentrates at 50 and 100 µg/mL. Anti-inflammatory IL-10 expression was significantly upregulated in LPS-stimulated macrophages by cranberry concentrates at 100 µg/mL after 24 hours of exposure. M1 polarization significantly decreased when LPS-stimulated macrophages were exposed to cranberry concentrates. High levels of positive M1 macrophages were present in all untreated control groups. M2 polarization significantly increased at all LPS-stimulated macrophages exposed to cranberry concentrates for 1 and 24 hours. CONCLUSION: Cranberry-derived proanthocyanidins may have the potential to act as an anti-inflammatory component in the therapy of periodontal and peri-implant diseases.
