Role of IL-18 Levels in Disease Activity and Cardiovascular Risk in Psoriatic Arthritis and Ankylosing Spondylitis

Elevated levels of interleukin (IL)-18 are associated with higher disease activity and cardiovascular risk in patients with psoriatic arthritis (PsA), but not ankylosing spondylitis (AS), according to study results published in Journal of Clinical Medicine.

Previous studies have shown that patients with PsA have a higher cardiovascular risk than those with AS. Researchers also hypothesized that IL-18 may play a key role in linking cardiovascular outcomes and inflammation in PsA and explaining the differences in cardiovascular risk profiles between PsA and AS.

Researchers assessed the association between IL-18 and cardiovascular disease activity in patients with PsA (including peripheral PsA and axial PsA) and AS.

Adult patients with PsA and AS were enrolled to participate in the study. Disease activity was measured using standard indices. Peripheral blood samples were collected for lipid profile analysis (total cholesterol, triglycerides, low-density cholesterol [LDL], high-density cholesterol [HDL], and C-reactive protein [CRP]). Cytokines (IL-18 and IL-17) were measured using an enzyme-linked immunosorbent assay (ELISA). The atherogenic index (AI), which is an in indicator of cardiovascular risk, was calculated using the formula AI=total cholesterol/HDL.

Among 155 patients, 94 had AS and 61 had PsA (47 with peripheral PsA and 14 with axial PsA). Levels of IL-18 were 160 pg/mL, 118 pg/mL, and 80 pg/mL among patients with peripheral PsA, axial PsA, and AS, respectively.

Among patients with PsA, IL-18 was positively correlated with AI (rho=0.46; P <.001) and triglyceride levels (rho=0.4; P <.001), and negatively correlated with HDL (rho=-0.37; P =.004). In a subset of patients with both PsA and ischemic heart disease, IL-18 showed stronger correlations: IL-18 was positively correlated with AI (rho=0.671; P =.004), triglyceride levels (rho=0.675; P =.001), and disease activity (rho=0.613; P =.023), and negatively correlated with HDL (rho=-0.608; P =.03).

Patients with peripheral PsA had the highest IL-18 levels, cardiovascular risk, and frequency of hypertriglyceridemia and ischemic heart disease. These patients also showed positive correlations between IL-18 and IL-17 (rho=0.47; P =.002), triglycerides (rho=0.45; P =0.01), and AI (rho=0.63, P =.021). In this group, linear regression models showed that IL-17, triglycerides, and tender joint count were associated with IL-18.

Limitations of the study included the prospective study design and a low number of study participants.

The researchers concluded, “We confirmed that patients with [peripheral PsA] are characterized by a more pronounced proinflammatory and proatherogenic cardiovascular risk profile than patients with [axial PsA] 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.”

Reference

Bonek K, Kuca-Warnawin E, Kornatka A, et al. Associations of IL-18 with altered cardiovascular risk profile in psoriatic arthritis and ankylosing spondylitis. J Clin Med. Published online January 30, 2022. doi:10.3390/jcm11030766