Background Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to synovial proliferation as well as cartilage and bone destruction. Cytokine-mediated immunity plays an important role in the pathogenesis of RA. Over the last years, several studies suggested evidences that the interleukin-33 (IL-33) and its soluble ST2 (sST2) have functions in the inflammatory process that lead to arthritis. Especially, IL-33 was recognized to perform as an inflammatory cytokine, exerted profound effects in human RA and experimental inflammatory arthritis. Therefore, the targeting of IL-33 has been proposed as a potential therapeutic approach and serum marker of treatment for RA.
Objectives The aim of this study was to investigate the clinical significance of serum IL-33 and sST2 level according to anti-TNF-α therapy in RA.
Methods We included 24 RA patients who treated with TNF-α inhibitors in Hanyang University Hospital between 2010 and 2011. We collected demographic findings, laboratory findings such as white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and total arthritic joint counts before and 12 weeks after treatment of TNF-α inhibitors. And we measured serum IL-33 and sST2 by using enzyme-linked immunosorbent assay. Twenty-six healthy subjects used as a control group for the serum levels of IL-33 and sST2.
Results RA patients (23 females and 1 male; mean age 45.2±13.5 years, mean disease duration 91.3±75.3 months) were treated with etanercept (54.2%), adalimumab (37.5%) or infliximab (8.3%). The mean levels of serum IL-33 were 199.8±107.4 pg/mL of baseline in RA patients, 213.5±327.5 pg/mL in RA patients after 12 weeks with anti-TNF-α therapy and 107.4±184.4 pg/mL in healthy controls. And the mean levels of serum sST2 were 260.1±303.8 pg/mL in RA patients before anti-TNF-α therapy, 181.6±185.8 pg/mL in RA patients after 12 weeks anti-TNF-α therapy, and 83.62±70.2 pg/mL in healthy controls. There was no statistical significance of serum IL-33 level between RA patients and healthy controls. The serum sST2 levels in RA patients before and after anti-TNF-α therapy were significantly higher than in controls (P<0.05). Although serum sST2 level showed decreasing trend according to anti-TNF-α therapy, there was no statistically significant difference in sT2 levels between baseline and 12 weeks therapy. The serum sST2 level correlated positively with WBC (r=0.408, P=0.010), ESR (r=0.383, P=0.016) and CRP (r=0.585, P<0.001). However, it had no correlation with total arthritic joint counts. The responders (n=19) to anti-TNF-α therapy had higher levels of sST2 compared to non-responders (n=5) to anti-TNF-α therapy, but without statistical significance.
Conclusions The serum sST2 level was increased in RA patients, and correlated with other inflammatory markers of disease activity. Monitoring of serum sST2 levels may be a possible marker of effectiveness to anti-TNF-α therapy for RA patients, when this is supported by an extended study with more patients.
Disclosure of Interest None declared