Cytokines in gingivocrevicular fluid of rheumatoid arthritis patients: A review of the literature

Abstract

Objective Rheumatoid arthritis (RA) and periodontitis share several pathological features including bone and soft tissue destruction and high levels of circulating inflammatory proteins. Studies related to cytokines in the periodontal inflammatory exudate (gingivocrevicular fluid, GCF) of RA patients might provide insight into the association between periodontitis and RA. The aim of our study was to review the literature on cytokines in GCF of RA patients including the effect of anti‐rheumatic treatment with biological disease‐modifying anti‐rheumatic drugs (DMARDs) and periodontal treatment on these cytokines. Materials and methods MedLine/PubMed searches with different combinations of keywords “rheumatoid arthritis or RA” and “crevicular fluid or GCF” until June 2019 revealed 64 articles. Ten cross‐sectional observational studies and nine treatment studies fulfilled the inclusion criteria. Results Rheumatoid arthritis patients have increased circulating and GCF levels of pro‐inflammatory cytokines and proteins, despite anti‐rheumatic treatment with biological DMARDs. Presence of periodontitis was accompanied by higher cytokine and protein levels. Treatment of periodontitis resulted in a decrease of these levels. Conclusion Analysis of GCF of RA patients reveals that the relationship between periodontitis and RA is bidirectional, probably caused by a non‐specific inflammatory burden. Data for a specific relationship are barely present in GCF.

Periodontal inflammation and distinct inflammatory profiles in saliva and gingival crevicular fluid compared with serum and joints in rheumatoid arthritis patients

“…In contrast to the more restricted profiles in saliva and GCF, we found that RA patients had a broader range of mediators in serum and joints, particularly Th1 and innate immune mediators. Consistent with previous studies, 29,30 our patients had reduced levels of the anti‐inflammatory cytokine, IL‐10, in GCF. In contrast with our findings, a prior study by Miranda et al.…”

“…In one study of 35 chronic RA patients, IL‐1β levels were elevated in saliva compared with those in healthy individuals (HIs), 27 while another study evaluating salivary TNF‐α levels in chronic RA patients did not find TNF‐α elevation 28 . Several studies of GCF in chronic RA patients, mainly those with periodontitis 29,30 revealed elevated levels of IL‐1β, TNF, MMP‐8, MMP‐9 and MMP‐13, and reduction in IL‐10, findings similar to those in non‐RA chronic periodontitis. GCF MMP‐8 and MMP‐9 levels in chronic RA patients with periodontitis tended to be even higher than in those with non‐RA chronic periodontitis 30 .…”

Effect of Anti-Rheumatic Treatment on the Periodontal Condition of Rheumatoid Arthritis Patients

“…This reduction in DAS28 was not related to the PISA or the presence of other intra-oral pathologies, such as caries and peri-apical pathology. On the contrary, periodontal treatment in RA patients was shown to clearly improve DAS28 scores and ESR levels, while other systemic inflammatory markers, such as CRP, IL-6, and TNF, tended to decrease [ 29 , 30 ].…”

Cytokines in gingival crevicular fluid in elderly rheumatoid arthritis patients in a population‐based cross‐sectional study: RANTES was associated with periodontitis

“…Two recent literature reviews have summarized studies performed in GCF in RA patients on cytokines, chemokines, enzymes, and tissue breakdown products stratified for periodontitis 8,9 . There were inconclusive results as to levels of interleukin‐1β (IL‐1β) in periodontitis in RA as summarized from several cross‐sectional studies, and the same levels of interleukin‐4 (IL‐4) and interleukin‐10 (IL‐10) between RA patients, periodontitis, and periodontally healthy patients 8,9 . Matrix metalloproteinase‐8 (MMP‐8), MMP‐9, and tumor necrosis factor alpha (TNF‐α) levels were higher in periodontitis and in RA and MMP‐8 levels increased with the severity of periodontitis 8,9 .…”