Interleukin-37 as an anti-inflammatory cytokine: does its relation to disease activity suggest its potential role in rheumatoid arthritis therapy?

Abstract

Background This study aimed to measure the serum and synovial interleukin (IL)-37 levels in rheumatoid arthritis (RA) patients compared to patients with primary knee osteoarthritis (PKOA) and healthy controls and to detect its relation to RA disease activity. Results This cross-sectional study included 50 RA patients with a mean age of 40.24 ± 8.62 years, 50 patients with PKOA with a mean age of 56.69 ± 4.21, and 40 healthy controls with a mean age of 41.75 ± 7.38 years. The mean serum IL-37 level in the RA patients (382.6 ± 73.97 pg/ml) was statistically significantly (P < 0.001) the highest among the studied groups; however, it showed a non-significant difference between the PKOA patients (70.38 ± 27.49 pg/ml) and the healthy controls (69.97 ± 25.12 pg/ml) (P > 0.94). Both serum and synovial IL-37 levels were significantly positively correlated with disease activity scores (r = 0.92, P< 0.001 and r = 0.85, P < 0.001), tender joint counts (r = 0.83, P < 0.001 and r = 0.82, P < 0.001 ), swollen joint counts (r = 0.72, P < 0.001 and r = 0.60, P < 0.001), visual analog scale (r = 0.82, P < 0.001 and r = 0.82, P < 0.001), erythrocyte sedimentation rate (r = 0.75, P < 0.001 and r = 0.65, P < 0.001), and C-reactive protein (r = 0.93, P < 0.001 and r = 0.79, P < 0.001), respectively. Conclusion Serum and synovial IL-37 were significantly elevated in the RA patients, and they were closely correlated. Being less invasive, the serum IL-37 could be a marker of disease activity and could reflect the effective disease control by drugs. Having an anti-inflammatory effect could not suggest IL-37 as the key player to control inflammation alone, but its combination with other anti-proinflammatory cytokines could be investigated.

Interleukin -37 in rheumatoid arthritis: Correlation with clinical severity and genetic polymorphisms in Mosul city, Iraq

“…This ranged from as low as (28.83 ng/l in RA and 11.84 in the controls) in one study 44 to as high as (712.40 ng/l in RA and 133.50 in the controls) in another study, 37 2) Some elements of the DAS 28 scoring system such as the number of tender and swelling joints and the overall health condition of the patients are largely subjected to personal judgement of the physicians which might affect the calculation of DAS28 score, 3) Differences in cohorts is another possibility, so a larger cohort might explore more positive correlation, 4) Most of the studies that reveled a positive correlation between IL-37 and DAS28 were carried on Asian populations (China) and only one study was reported among Arab population (Egypt). 45 Therefore, ethnicity is an important suggested factor to be considered when interpreting IL-37 results, 5) The concentration of IL-37 was observed to be significantly higher in the aspirated synovial fluid of RA patients than the circulation 45 and therefore synovial IL-37 might be a better marker to be considered when correlated with DAS 28 score, 6) Finally, in the current study we did not take into consideration the effect of the drugs on the IL-37 level which might be considered one of the limitations of this study. Therefore, further studies are suggested with larger cohorts to precisely compare the correlation between activity score and IL-37 taken into consideration the effects of anti-rheumatic drugs in those patients.…”