Abstract
Objective: To investigate the associations of IL-18 serum levels with serum lipids, cardiovascular risk, and disease activity in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with axial (axPsA) and peripheral (perPsA) joint involvement. Methods: 155 adult patients (PsA 61/AS 94) were enrolled in the study. Standard disease activity indices, BASDAI, and ASDAS, were calculated for AS and PsA and DAPSA for PsA. Sera from peripheral blood samples were obtained after night fasting. Serum concentrations of cytokines (IL-18, IL-17) were measured by ELISA, while lipid profile with total cholesterol (TC), triglycerides (TG), low-density cholesterol-(LDL), high-density cholesterol (HDL), and C-reactive protein (CRP) concentrations were determined using routine procedures. The atherogenic index was calculated using the standard formula AI = TC/HDL. Results: Patients with PsA and peripheral joint involvement (perPsA) had significantly higher IL-18 serum levels than axial PsA and AS patients (medians 160 vs. 116 vs. 80 pg/mL). In patients with PsA and in the subgroup with PsA+ ischemic heart disease (IHD), IL-18 positively correlated with atherogenic index (AI) (rho = 0.46 and rho = 0.67, respectively) and TG serum concentrations (rho = 0.4 and rho = 0.675), while negatively with HDL levels (rho = −0.37 and rho = −0.608). In PsA + IHD subgroup IL-18 serum levels correlated positively also with disease activity (DAPSA) (rho = 0.613). Importantly, in patients with perPsA, characterized by the highest IL-18 serum levels, cardiovascular risk, and frequency of both hypertriglyceridemia and IHD, positive correlations between IL-18 and IL-17 (rho = 0.47, p = 0.002), TG (rho = 0.45 p = 0.01) levels and AI (rho = 0.63 p = 0.021) were found. Whereas linear regression models revealed that IL-17, TG concentrations and the tender joint count had an impact on IL-18 Conclusions: We confirmed that patients with perPsA are characterized by a more pronounced proinflammatory and proatherogenic cardiovascular risk profile than patients with axPsA and AS. Importantly our study indicates that in PsA, but not in AS, elevated serum concentration of IL-18 is associated with higher disease activity and proatherogenic lipid profile, leading to a higher cardiovascular risk. Thus, our results point out IL-18 as a critical contributor in these pathological processes and possible therapeutic targets.
Highlights
Psoriatic arthritis (PsA) is a chronic condition associated with psoriasis (PsO), spondylitis and peripheral arthritis, and comorbidities, including cardiovascular disorders with an increased risk of death [1,2,3]
According to some recent reports, high serum levels of IL-18 in PsA are associated with arthritis and skin inflammation [12,13] and with an increased level of IL-17 [14], an interleukin playing a key role in the pathogenesis of axial of SpA [15,16]
The diagnosis was based on the criteria for the Classification of Psoriatic Arthritis (CASPAR) [23], and the diagnosis of ankylosing spondylitis (AS) was based on the Assessment of Spondyloarthritis International Society (ASAS) criteria for axial spondyloarthritis with X-ray changes [24]
Summary
Psoriatic arthritis (PsA) is a chronic condition associated with psoriasis (PsO), spondylitis and peripheral arthritis, and comorbidities, including cardiovascular disorders with an increased risk of death [1,2,3]. According to some recent reports, high serum levels of IL-18 in PsA are associated with arthritis and skin inflammation [12,13] and with an increased level of IL-17 [14], an interleukin playing a key role in the pathogenesis of axial of SpA [15,16]. It is justified to undertake research to verify the hypothesis about the role of IL-18 as a potential “keystone” linking increased cardiovascular risk with active inflammation in PsA. We have investigated whether IL-18 could be responsible for the differences in cardiovascular risk profiles between PsA and AS
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