Periodontitis is a frequent local inflammatory disease. The microbiota and repeated exposure to bacterial endotoxins triggers excessive inflammation through oral mucosal immunity, sometimes leading to a destructive effect on the supportive mucosal tissues around the teeth. Elimination of the pathogens and increasing the tolerance of the cellular immune response is crucial in addition to standard dental therapies like mechanical debridement. Based on our experience on immune-mediated diseases, especially primary immunodeficiency diseases (PIDs), we wrote this review to discuss the treatment alternatives for severe periodontal disease. Risk factors are malnutrition, vitamin deficiencies, smoking, systemic inherited and acquired immune-mediated diseases, infections, endocrinological diseases, and pharmacological agents may accompany periodontitis. The diagnosis and treatment of dietary deficiencies, as well as the addition of nutritional supplements, may aid in epithelial regeneration and immune system function. Recently, modifications to the therapeutic option for severe periodontitis have been made depending on the fact that the immune response against bacteria may modify the severity of periodontal inflammation. The anti-inflammatory therapies support or inhibit the host's immune response. The clinical approach to severe periodontitis should extend beyond classical therapies. There is a need for a diverse therapeutic strategy that supports the epithelial barrier, which is the crucial component of innate immunity against microbiota. Leukocytes are the main cellular component in periodontal inflammation. Anti-inflammatory therapeutic options directed at leukocytes, such as IL-17 and IL-23-targeted therapies, could be the candidates for the treatment of severe periodontitis. Therapy against other inflammatory cytokines, IL-1, IL-6, IL12, IL23, TNF-alpha, PGE2, and cytokine receptors, could also be used in periodontal inflammation control.
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