Background Inflammatory spondyloarthropathies (SpAs), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are associated with cardiovascular (CV) disorders. In both diseases cytokines of IL-17/IL-23 axis are thought to play a pathogenic role. PsA, but not AS, is usually preceded by psoriasis, suggesting contribution of skin inflammation-related cytokines to disease manifestation and CV risk.
Objectives To search in AS and PsA patients for the association between CV risk and serum concentrations of select cytokines, i.e. of IL-17/IL-23 axis, IL-18 and osteoprotegerin (OPG) related to skin inflammation and/or cardiovascular disease (CVD) pathogenesis, respectively.
Methods Twenty patients with AS (15M/5F) and 18 patients with PsA (10M/8F) of similar age (mean±SD, 42±7 vs 46±10 years) and disease duration (6.5±10 vs 6.1±7 years) were evaluated. A group of 38 sex and age-matched healthy volunteers was used as a control. Routine laboratory tests, i.a. measurement of serum C-reactive protein (CRP) concentrations were performed. Clinical data, including evaluation of disease activity by ASDASCRP and BASDAI indices, calculation of SCORE (Systemic Coronary Risk Evaluation) index and atherogenic index (AI=total cholesterol/HDL) were collected. Serum concentrations of IL-17AF, IL-21, IL-23, IL-27, IL-18 and OPG were measured by specific commercially available enzyme-linked immunosorbent assays (ELISA) and were expressed in pg/ml. The Mann-Whitney U-test was applied for intergroup comparison, and correlation was assessed using a Spearman's Rank two-tailed test (R value is shown).
Results Compared with control, total group of SpAs patients was characterized by significantly elevated serum concentrations of OPG (1757±852 vs 1062±406 pg/ml), IL-18 (273±235 vs 164±195 pg/ml) and IL-21 (68±127 vs 20±49 pg/ml). Interestingly, while up-regulation of OPG (1517±387) and IL-18 (324±291) was attributed to PsA, IL-21 increase (90.6±158) was found in AS group. Nevertheless, there was no significant difference between patients' groups in the tested cytokines concentrations. Despite of less active disease in PsA than in AS patients (ASDASCRP 2.76±1 vs 3.44±0.89), PsA patients had higher AI (4.44±1.3 vs 3.37±1). Importantly, in both AS and PsA groups, OPG concentration positively correlated with SCORE values (R=0.613 and 0.792, respectively). However, in PsA patients also IL-18 concentration showed similar noxious associations, correlating positively with AI (R=0.705), and triglycerides level (R=0.679) but inversely with HDL level (R= - 0.525) and HDL/LDL ratio (R= -0.623). On the other hand, neither in AS nor in PsA patients the cytokines of IL-17/IL-23 axis were significantly related to CV risk.
Conclusions By showing positive correlation of serum OPG with CV risk expressed by SCORE in AS and PsA patients we support opinion of an important role of OPG in CVD pathogenesis. Our results may also suggest that in PsA patients IL-18, up-regulated owing to skin inflammation, contributes to dyslipidemia and thus further increases CV risk.
Acknowledgements Supported by the NIGRiR, Warsaw, Poland (grants No S/16 and S/2).
Disclosure of Interest None declared