Background Rheumatoid arthritis (RA) is an independent risk factor for early cardiovascular disease (CVD) and mortality. Traditional risk factors and inflammation inherent to the disease are implicated in endothelial dysfunction and cardiovascular events in RA.1 Interleukin 33 (IL-33) is a cytokine related to amplification of the articular inflammation, in animal models. Elevated IL-33 serum levels have been described in RA patients, suggesting a possible participation in the disease's physiopathology.2,3 The role of IL-33 in cardiovascular events is also under investigation and it seems that this cytokine has a protective effect regarding the development of atherosclerosis.4
Objectives Verify the association of the serum levels of IL-33 and its soluble receptor (sST2) with carotid subclinical atherosclerosis in a group of RA patients.
Methods Cross-sectional observational study in which RA patients, free from atherosclerotic CVD, were submitted to clinical and laboratorial evaluation. Carotid high-resolution ultrasonography evaluated the presence of atherosclerotic plaques and the intima-media thickness (IMT) of common carotid artery wall. IL-33 and sST2 serum levels were measured by ELISA.
Results 102 patients were included, 92,5% women, with mean age of 55,5 (±10) years and mean disease duration of 17,6 (±9,5) years. Eighty-four (82,4%) patients had seropositive RA. The prevalence of carotid plaque was 23,5% and the median of IMT was 0,7 (0,6–0,8) mm. An increase of 0,1 mm in IMT increased by 5,3 times the chance of plaque (CI95%: 2,88–983,37) and each additional year of RA duration increased by 6% the chance of plaque presence (IC95%: 1,01–1,12). Each additional year of age and each additional unit in cardiovascular risk score (Framingham) increased by 0,003 mm and 0,012 mm, respectively, the IMT (CI95%: 0–0,007 and 0,007 – 0,016). MTX use was associated with a reduction of 0,07 mm in IMT (CI95%: -0,117– -0,013). Sixty-eight (66,7%) patients had IL-33 serum levels above the detection limit with a median value of 69,1 (31,6–114,5) pg/mL. The median sST2 serum level was 469,8 (336,3–651) pg/mL. There was not association between IL-33 nor sST2 serum levels with IMT or plaque.
Conclusions IL-33 and sST2 serum levels were not associated with subclinical atherosclerosis, estimated by IMT measurement and search of carotid plaques. Traditional risk factors for atherosclerosis (age and cardiovascular risk score) and disease duration were associated with IMT and presence of plaque, while MTX was related to smaller intima-media thickness.
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Xu D, Jiang HR, Li Y, et al. IL-33 exacerbates autoantibody-induced arthritis. J Immunol 2010;184(5):2620-2626.
Matsuyama Y, Okazaki H, Tamemoto H, et al. Increased levels of interleukin 33 in sera and synovial fluid from patients with active rheumatoid arthritis. J Rheumatol 2010;37(1):18-25.
Kunes P, Holubcová Z, Kolácková M, Krejsek J. The counter-regulation of atherogenesis: a role for interleukin-33. Acta Medica (Hradec Kralove) 2010;53(3):125-129.
Disclosure of Interest None declared
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