Coordinate production of PGE, and IL‐1β in the gingival crevicular fluid of adults with periodontitis: its relationship to alveolar bone loss and disruption by twice daily treatment with ketorolac tromethamine oral rinse

Abstract

The inflammatory mediators prostaglandin E2 (PGE2) and interleukin‐1β (IL‐1β) play critical roles in the inflammatory process leading to alveolar bone and connective tissue loss in periodontal disease. Data from a previously published 6‐month clinical study demonstrated that twice daily use of 0.1% ketorolac tromethamine oral rinse prevented alveolar bone loss in adults with periodontitis. We further analyzed data from this study to examine the relationship between PGE2, IL‐1β and bone loss. Patient mean PGE2, and IL‐1β levels in gingival crevicular fluid (M‐GCF) measured throughout the course of the study were directly compared to the maximum amount of alveolar bone height loss observed at a single study site in each patient. The maximum amount of bone loss measured was chosen for the analysis since the pattern of bone loss was clearly episodic in nature. A statistically significant correlation (r = 0.73, p = 0.001) exists between M‐GCF PGE2 concentration and the maximum amount of bone height lost at individual patient study sites. The correlation between M‐GCF IL‐1β concentration and maximum bone height lost is also statistically significant (r = 0.66, p = 0.005). Over the 6‐month duration of the study, both PGE, and IL‐1β were coordinately expressed in the placebo treatment group as reflected in the significant correlation between M‐GCF concentrations of the 2 mediators (r=0.81, p<0.001). Treatment of patients with 0.1% ketorolac tromethamine twice daily for 6 months resulted in reductions of PGE, in GCF and a negligible correlation between M‐GCF PGE, and M‐GCF IL‐1β (r=0.42, p=0.088). This lack of a strong association between the 2 mediators in the ketorolac treatment group provides a direct biochemical readout of the anti‐inflammatory efficacy of ketorolac tromethamine oral rinse in patients with periodontitis. Further studies are warranted to determine the full diagnostic potential of M‐GCF levels of PGE2, and IL‐1β for predicting risk of alveolar bone loss in patients with periodontitis and monitoring periodontal therapy effectiveness.

Interleukin‐1 Gene Polymorphisms and Chronic Periodontitis in Adult Whites: A Systematic Review and Meta‐Analysis

“…4 Clinically, elevated IL-1 levels, primarily IL-1b, have been associated with many human diseases, and higher gingival fluid levels of IL-1 have been associated with periodontitis severity. [5][6][7] Blocking IL-1 activity is currently the standard therapy for autoinflammatory diseases in which the monocyte macrophage is the dominant effector cell, 8 and specific IL-1 and TNF blocking drugs in animal models show that IL-1 is a critical mediator in the pathogenesis of periodontitis. 9 The human IL-1 system comprises at least 11 genes for IL-1-type ligands mainly clustered on chromosome 2q14, 10 with two other genes, IL-18 and IL-33, on chromosomes 11 and 9, respectively.…”

“…The interleukin‐1 (IL‐1) cytokine family has key regulatory roles in innate and adaptive immunity and in pathogenesis of infectious, autoimmune, and autoinflammatory diseases, as well as mediating systemic inflammatory responses comprising fever, hepatic acute‐phase proteins, and leukocyte activation 4 . Clinically, elevated IL‐1 levels, primarily IL‐1β, have been associated with many human diseases, and higher gingival fluid levels of IL‐1 have been associated with periodontitis severity 5‐7 . Blocking IL‐1 activity is currently the standard therapy for autoinflammatory diseases in which the monocyte macrophage is the dominant effector cell, 8 and specific IL‐1 and TNF blocking drugs in animal models show that IL‐1 is a critical mediator in the pathogenesis of periodontitis 9 …”

Comparison of Clinical, Radiographic, and Immunologic Inflammatory Parameters around Crestally and Subcrestally Placed Dental Implants: 5‐Year Retrospective Results

“…[50][51][52] Likewise, MMP-9 (also known as type IV collagenase) plays an active role in the degradation and remodeling of the extracellular matrix. 53 High concentrations of IL-1β and MMP-9 have been reported in the gingival crevicular fluid (GCF) of patients with periodontitis, 54,55 and assessment of proinflammatory cytokines in the GCF has been proposed to have diagnostic potential for patients with periodontitis. The authors of this study suggest that assessment of proinflammatory cytokines (such as IL-1β and MMP-9) in the PICF may also hold diagnostic potential for patients with peri-implant inflammation.…”

Daytime variations of interleukin‐1β in gingival crevicular fluid

“…It is one of the most potent osteoclast-activating factors within the human organism and is thus believed to play an important role in periodontal tissue breakdown (4,5). Indeed, numerous studies report increased concentrations of IL-1b in gingival crevicular fluid (GCF) at sites with gingivitis or periodontitis (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Furthermore, the level of crevicular IL-1b is found to increase during experimental gingivitis (25)(26)(27)(28)(29)(30) and to decrease after periodontal therapy (31)(32)(33)(34), even though data on the latter aspect are equivocal (35,36).…”