Association of cytokine patterns and clinical/laboratory parameters, medication and periodontal burden in patients with rheumatoid arthritis (RA)

Abstract

To evaluate serum levels of the following cytokines in rheumatoid arthritis subjects with periodontal disease: Interleukin-6,-10,-17, and-23. Patients with rheumatoid arthritis frequently suffer from periodontal disease. Both diseases partly result from a dysregulated immune response. The current study aimed to quantify Interleukin-6,-10,-17, and-23 levels in rheumatoid arthritis. It should be investigated if the periodontal disease would have additional modifying effects. A total of 157 patients were included. Serum levels of IL-6,-10,-17, and-23 were measured by ELISA. Serum IL-10 increased with longer duration of morning stiffness and with higher rheumatoid factor and anti-cyclic citrullinated peptide titres. IL-10 was also elevated with longer duration of prednisolone (< 5 mg daily) and leflunomide therapy. Subjects with lower erythrocyte sedimentation rate/longer leflunomide therapy displayed more missing teeth/more clinical attachment loss. IL-17 was higher in subjects with fewer missing teeth if the following criteria were fulfilled: shorter prednisolone (< 5 mg) and methotrexate therapy, more swollen joints, longer morning stiffness. IL-23 finally was increased in subjects with higher rheumatoid factor and in those with higher periodontal probing depth/clinical attachment loss in the following situations: lower rheumatoid factor and shorter leflunomide therapy. Subjects suffering from dental/periodontal burden show an aberrant systemic cytokine availability of serum IL-6, IL-10, IL-17 and IL-23 related to disease activity and medication. This examination underlines the complexity of potential interactions between disease activity and medication related to periodontal burden.

IL‐23/IL‐17 axis and soluble receptors isoforms sIL‐23R and sIL‐17RA in patients with rheumatoid arthritis‐presenting periodontitis

“…Regarding these findings, Ridgley LA et al 39 proposes that the expression of some cytokines, such as IL‐17A, is inversely proportional to the course and chronicity of arthritis rheumatoid and IL‐17 is expressed mainly in the preclinical phase and decreases according to the chronicity of RA. Moreover, the IL‐17A levels in RAP patients are diminished when they have high disease activity (DAS28‐ESR), according to Patschan S et al 29 Interestingly, the P and RAP group showed similar behavior since IL‐17A decreases when an advanced periodontitis stage is found (Stage III). This suggests that IL‐17 tends to modulate its expression downward as disease activity progresses in RAP.…”

“…In this context, IL‐23/IL‐17 axis in RA and P has also been studied in different samples, 13–22 as well as its receptors, IL‐23R, and IL‐17RA 23–26 . In patients with rheumatoid arthritis who present periodontitis, IL‐17 has been reported in the gingival crevicular fluid (GCF) and serum, 27 while IL‐23 has been reported in saliva, 28 likewise IL‐23 and IL‐17 in serum 29 . It has also been described that IL‐23 and IL‐17 levels in GCF, saliva, serum, and plasma are elevated in both periodontitis patients and 17,18,20–22,24 patients with rheumatoid arthritis 13,15,16,25,27,30,31 …”

“…[23][24][25][26] In patients with rheumatoid arthritis who present periodontitis, IL-17 has been reported in the gingival crevicular fluid (GCF) and serum, 27 while IL-23 has been reported in saliva, 28 likewise IL-23 and IL-17 in serum. 29 It has also been described that IL-23 and IL-17 levels in GCF, saliva, serum, and plasma are elevated in both periodontitis patients and 17,18,[20][21][22]24 patients with rheumatoid arthritis. 13,15,16,25,27,30,31 Therefore, we hypothesize that IL-23 and IL-17A levels, as well as their soluble receptors, are elevated in patients with both pathologies.…”

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

“…Currently, while csDMARDS and biological DMARDS have shown their efficacy in the treatment of RA, insufficient evidence is available to estimate the effect of such anti-rheumatic treatment on the periodontal condition of RA patients [ 11 , 12 ]. There is some evidence that treatment with anti-TNF might initially improve bleeding on probing and the gingival index, and later on it might improve bleeding on probing pocket depth and clinical attachment level [ 13 ].…”

Tooth Loss Is Associated with Disease-Related Parameters in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis—A Cross-Sectional Study

“…A higher prevalence of tooth loss in individuals suffering from RA has already been presumed in previous studies [ 8 , 21 , 22 , 23 ]. Furthermore, missing teeth were found to be a potential influential factor on proinflammatory cytokines in RA patients [ 24 ]. Additionally, a Japanese study reported tooth loss to be related to stronger RA therapies (medication), independent of the disease activity of RA [ 6 ].…”