Cyclophosphamide-induced immunomodulation as a potential modifier of apical periodontitis: a hypothesis-based study

Cyclophosphamide (CPD) is a widely used antineoplastic and immunosuppressive agent with well-established effects on adaptive immunity, particularly through the modulation of T lymphocyte populations. Objective: This study aimed to discuss the hypothesis that CPD-mediated immunomodulation may modify the development and progression of apical periodontitis (AP), influencing disease expression, bone resorption, and periapical healing. Material and Methods: A consultation of the scientific literature was conducted to develop and adequately support the proposed hypothesis. Articles related to the topic were identified using keywords referring to cyclophosphamide, apical periodontitis, immunomodulation, and T lymphocytes. The evidence retrieved was analyzed and integrated by considering the immunomodulatory effects of CPD, the immunopathogenesis of AP, and the role of T lymphocyte subsets in the regulation of inflammation, cytokine production, bone resorption, and tissue repair. Results: The available evidence indicates that CPD exerts dose-dependent immunomodulatory effects, including the selective regulation of regulatory T lymphocytes. T lymphocytes play a central role in the complex immune response involved in AP by influencing cytokine production, inflammatory regulation, and the balance between bone resorption and repair. Therefore, CPD-induced alterations in T lymphocyte subsets may modify the inflammatory response associated with AP and, consequently, influence its development, progression, and healing. Conclusion: CPD-mediated immunomodulation is biologically plausible as a potential modifier of AP. Experimental and clinical studies are needed to test this hypothesis and determine its implications for the diagnosis, treatment, and follow-up of endodontic diseases in patients undergoing CPD therapy. KEYWORDS Apical periodontitis; Cyclophosphamide; Endodontics; Immunomodulation; T lymphocytes.