Molecular cytokine-dependent mechanisms of periodontitis pathogenesis and the potential for pharmacological IL-1 modulation in disease treatment

Abstract

Periodontitis (P) is one of the most common human dental diseases, with significant medical and social implications. According to the World Health Organization, more than 45% of the adult population worldwide exhibits clinical signs of periodontitis, with 10%–15% of cases becoming generalized with destruction of the alveolar bone. This review presents the results of modern research demonstrating that the etiopathogenesis of periodontitis is not limited to local microbial factors; systemic, social, and behavioral factors can play a significant role, determining the body's susceptibility to chronic inflammation. In this study, we focus on the role of cytokines in the athogenesis of periodontitis. Based on modern research, we demonstratethe general biological significance of cytokines and their role in initiating periodontal inflammation and systemic diseases associated with periodontitis. The molecular and biochemical cytokine-dependent mechanisms of initiation and progression of oxidative stress in periodontitis are covered in detail. The role of individual cytokines in the pathogenesis of periodontitis is shown: interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF-α), interferon-gamma, IL-10, IL-23, IL-17, and Th17 cells. The review presents a modern approach to complex drug therapy of periodontitis. The arsenal of antiseptics, antibiotics, and synthetic antimicrobial agents available to dentists is presented. A new approach is demonstrated in the use of probiotics—live microorganisms (probiotics, symbiotics, and bacteriophages) that maintain the balance of the oral microbiome. Beyond standard antimicrobial and anti-inflammatory therapies, host modulators, antioxidants, and bioregulatory agents play a vital role in treating P. They effectively suppress proinflammatory cytokines, mitigate oxidative stress, and improve metabolic activity in affected tissues. We present data on the development of individual regenerative structures using bioactive polymers and 3D printing for the future treatment of chronic periodontitis, as well as the potential use of biomaterials with nanostructured components, collagen matrices with nanoparticles, hydrogels with functional peptides, synthetic polymers with a modest antibacterial effect, and transplantation of mesenchymal stem cells, as well as bioactive scaffolds with stem cells. The most important section of the review is devoted to the clinical and pharmacological properties of cytokine modulators—TNF-α blockers, IL-6 blockers, and IL-1 blockers. Using current research results, including our own, we demonstrate the potential of using an IL-1 receptor antagonist and its new dosage form, such as a dental gel.