Table 1.
Studies on cytokines in gingivocrevicular fluid (GCF) of patients with rheumatoid arthritis (RA) and systemically healthy controls (HC) with (+) or without (−) chronic periodontitis (CP)
| Study | Patients (number) | Sex (M/F) | Age (years, mean ± SD) | RA duration (years, mean ± SD) | RA treatment (number of patients) | Cytokine(s) investigated in GCF | Same cytokine(s) investigated in serum | Periodontal assessment | Periodontal classification | Differences in periodontal status between study groups | Differences in concentrations of cytokines in GCF between study groups | Differences in concentrations of cytokines in serum between study groups |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bender et al., (2019) | RA (10) | 2/8 | 63 ± 12 | 11 (range 2–22) | no detailed information provided | IL1‐β, MCP−1, MCP−3 | no | PSR, number of teeth, sites with PD > 5mm | Armitage 1999 |
RA significantly less teeth compared to HC + CP and HC‐CP HC + CP significantly higher PSR and sites with PD > 5 mm compared to RA and HC‐CP |
Significantly higher amount of IL1‐β in RA compared to HC‐CP (no concentration assessed) No difference in amount of MCP−1 and MCP−3 between all study groups |
– |
| HC + CP (10) | 4/6 | 57 ± 11 | – | – | ||||||||
| HC‐CP (10) | 7/3 | 38 ± 8 | – | – | ||||||||
| Kirchner et al., (2017) |
RA (103, +CP in 65%) |
45/58 | 56 ± 11 | 11 ± 6 | MTX (65), leflunomide (18), chloroquine (10), sulfasalazine (5), biological DMARDs (21), steroids (61) | MMP−8 | no | PD, BOP, CAL | Page & Eke, 2007 | RA versus HC: PD, BOP, CAL significantly higher in HC | RA + CP versus HC + CP: significantly higher in RA + CP | – |
|
HC (104, +CP in 79%) |
36/68 | 57 ± 12 | – | – | RA‐CP versus HC‐CP: no significant difference | |||||||
| Silosi et al., (2015) | RA + CP (12) | 3/9 | n.a. (range 38–62) | n.a. | no detailed information provided | MMP−9 | yes | PD, BOP, CAL, PI | ≥4 teeth with PD > 6mm on both maxillaries and radiographic evidenceof bone loss | n.a. | RA + CP versus HC + CP: significantly higher in RA + CP | RA + CP versus HC + CP: significantly higher in RA + CP |
| HC + CP (14) | 6/8 | n.a. (range 39–68) | ‐ | ‐ | ||||||||
| Cetinkaya et al., (2013) | RA (17) | 3/14 | 48 ± 11 | 6 ± 6 | MTX + sulfasalazine (15), leflunomide (2) | IL1‐β, IL−4, IL−10, TNF‐α | yes (only IL1‐β and IL−10) | PD, CAL, GI, PI | Armitage 1999 | RA versus HC + CP: PD, CAL, GI significantly higher in HC + CP | RA versus HC + CP: no significant differences of all assessed cytokines | RA versus HC + CP: significantly higher Il−1β in HC + CP |
| HC + CP (16) | 10/6 | 44 ± 7 | – | – | RA versus HC‐CP: PD, CAL, GI significantly higher in RA | RA versus HC‐CP: all assessed cytokines significantly higher in HC‐CP | RA versus HC‐CP: significantly higher Il−1β in HC‐CP | |||||
| HC‐CP (16) | 8/8 | 28 ± 6 | – | – | HC + CP versus HC‐CP: PD, CAL, GI significantly higher in HC + CP | HC + CP versus HC‐CP: all assessed cytokines significantly higher in HC‐CP | HC + CP versus HC‐CP: no significant differences | |||||
| Gümüş et al., (2013a) and (2013b) | RA + CP (17) | 0/17 | n.a. (range 25–64) | n.a. | no detailed information provided | IL−17, RANKL, OPG, TNF‐α, APRIL, BAFF | yes | PD, BOP, CAL, PI | not specified | RA + CP versus HC + CP: only PD significantly higher in RA + CP | RA + CP versus HC + CP: significantly higher RANKL, Il−17, TNF‐α, APRIL, BAFF in RA + CP | RA + CP versus HC + CP: significantly higher RANKL, Il−17, TNF‐α, APRIL, BAFF in RA + CP, significantly higher OPG in HC + CP |
| HC + CP (13) | 0/17 | n.a. (range 41–66) | – | – | ||||||||
| Biyikoğlu et al., (2009) | RA (25) | 6/19 | 54 ± 10 | 18 ± 10 | MTX + prednisolone | MMP−8, MMP−13, TIMP−1 | no | PD, BOP, CAL, PI | Armitage 1999 | RA versus HC + CP: no differences in PD, BOP, CAL, PI | RA versus HC + CP: no significant differences | ‐ |
| HC + CP (25) | 14/11 | 50 ± 8 | – | – | RA versus HC‐CP: PD, BOP, CAL, PI significantly higher in RA | RA versus HC‐CP: significantly higher concentration of MMP−8 in RA | ||||||
| HC‐CP (24) | 12/12 | 49 ± 7 | – | – | HC + CP versus HC‐CP: PD, BOP, CAL, PI significantly higher in HC + CP | HC + CP versus HC‐CP: significantly higher MMP−8 in HC + CP | ||||||
| Miranda et al., (2007) | RA (17) | 2/15 | 50 ± 11 | 12 ± 10 | NSAIDs, MTX, sulfasalazine, prednisolone | IL1‐β, IL−18, neutrophil elastase | no | PD, BOP, CAL, GI, PI | n.a. | RA versus HC: no significant differences in PD, BOP, CAL, GI, PI | Significantly higher amount (no concentration assessed) of Il−1β in HC | – |
| HC (17) | 2/15 | 49 ± 11 | – | – | ||||||||
| Biyikoğlu et al., (2006) | RA (23) | 5/18 | 53 ± 10 | 16 ± 10 | MTX + prednisolone | IL1‐β, PGE2 | no | PD, BOP, CAL, PI | Armitage 1999 | RA versus HC + CP: no significant differences in PD, BOP, CAL, PI | No significant differences between all study groups | ‐ |
| HC + CP (17) | 9/8 | 49 ± 7 | – | – | RA versus HC‐CP: PD, BOP, CAL, PI significantly higher in RA | |||||||
| HC‐CP (17) | 3/14 | 41 ± 7 | – | – | HC + CP versus HC‐CP: PD, BOP, CAL, PI significantly higher in HC + CP | |||||||
| Bozkurt et al., (2006) | RA + CP (17) | 5/12 | 47 ± 11 | n.a. | prednisolone, indomethacin, chloroquine | IL−4, IL−10 | no | PD, CAL, GI, PI | CAL > 2 mm at > 2 sites at in > 3 teeth per quadrant and radiographic evidence of bone loss | RA + CP versus HC + CP: only PD significantly higher in HC + CP | RA + CP versus HC + CP: Il−4 significantly higher in RA + CP | – |
| HC + CP (17) | 11/6 | 44 ± 10 | – | – | RA + CP versus HC‐CP: PD, CAL, GI, PI significantly higher in RA | RA + CP versus HC‐CP: both cytokines significantly higher in HC‐CP | ||||||
| HC‐CP (17) | 9/8 | 36 ± 4 | – | – | HC + CP versus HC‐CP: PD, CAL, GI, PI significantly higher in HC + CP | HC + CP versus HC‐CP: both cytokines significantly higher in HC‐CP | ||||||
| Bozkurt et al., (2000) | RA + CP (15) | 9/6 | 48 ± 7 | n.a. (range 1–8 years) | prednisolone, indomethacin, chloroquine | IL−6 | no | PD, CAL, GI, PI | not specified | RA + CP versus HC + CP: only PI significantly higher in RA | No significant differences between all study groups | – |
| HC + CP (15) | 11/4 | 47 ± 7 | – | – | RA + CP versus HC‐CP: PD, CAL, GI, PI significantly higher in RA | |||||||
| HC‐CP (15) | 8/7 | 46 ± 7 | – | – | HC + CP versus HC‐CP: PD, CAL, GI, PI significantly higher in HC + CP |
Abbreviations: APRIL, a proliferation inducing ligand; BAFF, B cell activating factor; BOP, bleeding on probing; CAL, clinical attachment level; DMARDs, disease‐modifying anti‐rheumatic drugs; GI, gingivitis index; IL, interleukin; MCP, monocyte chemoattractant protein; MMP, matrix metalloproteinase; MTX, methotrexate; n.a., not assessed; NSAIDs, non‐steroidal anti‐inflammatory drugs; OPG, osteoprotegerin; PD, periodontal pocket depth; PGE2, prostaglandin E2; PI, plaque index; PSR, Periodontal screening and recording index (Lo Frisco et al., 1993) Armitage 1999 (Armitage, 2000), Page and Eke (Page & Eke, 2007); RANKL, receptor activator of nuclear factor‐kappa β ligand; TIMP, tissue inhibitor of MMP; TNF‐α, tumor necrosis factor‐α.