Host defense peptide IDR-1002 associated with ciprofloxacin as a new antimicrobial and immunomodulatory strategy for dental pulp revascularization therapy

Regenerative therapies such as dental pulpal revascularization appear as an option for traumatized immature permanent teeth. However, the triple antibiotic paste TAP (metronidazole, minocycline, and ciprofloxacin), used for these therapies, can generate cytotoxicity and dentin discoloration. In contrast, host defense peptides (HDPs) are promising antimicrobial and immunomodulatory biomolecules for dentistry. This study aimed to evaluate in vitro the antimicrobial activity (against Staphylococcus aureus and Enterococcus faecalis) and the immunomodulatory potential (by the evaluation of IL-1 alpha, IL-6, IL-12, IL-10, TNF-alpha and NO, in RAW 264.7 macrophages and IL-6, TGF-beta and NO, in L929 fibroblast) of synthetic peptides (DJK-6, IDR-1018, and IDR1002), compared to TAP in an in vitro infection model containing heat-killed antigens from E. faecalis and S. aureus. Furthermore, the synergistic potential of ciprofloxacin and IDR-1002 was evaluated by checkerboard. Ciprofloxacin was the best antimicrobial of TAP, besides acting in synergism with IDR-1002. TAP was proinflammatory (p < 0.05), while the association of ciprofloxacin and IDR-1002 presented an anti-inflammatory profile mainly in the presence of both heat-killed antigens (p < 0.05). Based on these results, ciprofloxacin associated with IDR-1002 may demonstrate an efficient antimicrobial and immunomodulatory action in this in vitro model. Further in vivo studies may determine the real potential of this combination.