Influence of Gestational Hormones on the Bacteria-Induced Cytokine Response in Periodontitis

Abstract

Periodontitis is an inflammatory disease that affects the supporting structures of teeth. The presence of a bacterial biofilm initiates a destructive inflammatory process orchestrated by various inflammatory mediators, most notably proinflammatory cytokines, which are upregulated in the gingival crevicular fluid, leading to the formation of periodontal pockets. This represents a well-characterized microbial change during the transition from periodontal health to periodontitis; interestingly, the gestational condition increases the risk and severity of periodontal disease. Although the influence of periodontitis on pregnancy has been extensively reviewed, the relationship between pregnancy and the development/evolution of periodontitis has been little studied compared to the effect of periodontitis on adverse pregnancy outcomes. This review is aimed at summarizing the findings on the pregnancy-proinflammatory cytokine relationship and discussing its possible involvement in the development of periodontitis. We address (1) an overview of periodontal disease, (2) the immune response and possible involvement of proinflammatory cytokines in the development of periodontitis, (3) how bone tissue remodelling takes place with an emphasis on the involvement of the inflammatory response and metalloproteinases during periodontitis, and (4) the influence of hormonal profile during pregnancy on the development of periodontitis. Finally, we believe this review may be helpful for designing immunotherapies based on the stage of pregnancy to control the severity and pathology of periodontal disease.

Figure 1

Innate immune cells, including keratinocytes, polymorphonuclear cells (PMNs), antigen-presenting cells (APCs), and natural killer (NK) cells, hold pathogen recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs) present in biofilm bacteria, and these interactions promote the acute inflammatory response. Antigen-presenting cells (APCs) phagocytose pathogens, process antigens, and present the antigens in the form of peptides displayed by major histocompatibility complex (HLA) molecules. Costimulatory molecules stabilize this interaction. APCs migrate to secondary lymphoid tissues where they activate adaptive immune cells, including CD4⁺ T cells, such as Th1, Th2, and Th17 cells; cytotoxic CD8⁺ T cells; and B cells that will mature into antibody-producing plasma cells. Created with BioRender.com (https://biorender.com/).

Figure 2

Time course of pregnancy hormones, periodontal disease, and the proinflammatory cytokine MIF. During early gestation, hormones are produced in the corpus luteum, and later until the end of gestation, they are produced in the placenta. Estriol is also synthesized in the placenta, and its production ceases when the pregnancy reaches term. Therefore, embryo implantation and early gestation require a Th1 profile with the expression of proinflammatory cytokines. During the second half of gestation, the expression of these cytokines decreases, and the profile is a Th2 and Treg cell profile, which is maintained until delivery, when the profile returns to a Th1 profile. The expression of MIF, which is a proinflammatory cytokine, maintains this trend during pregnancy. Created with BioRender.com (https://biorender.com/).