Potential role of interleukin-18 in patients with rheumatoid arthritis-associated carotid intima-media thickness but not insulin resistance

Objective: Plasma interleukin-18 (IL-18) has been reported to be associated with homeostasis model assessment of insulin resistance (HOMA-IR). It also has been described as one of the factors that, in addition to insulin resistance, may also contribute to atherosclerosis. Parameters of systemic inflammation are also significantly associated with circulating IL-18. Our objective was to investigate whether IL-18 is associated with insulin resistance and atherosclerosis in patients with rheumatoid arthritis (RA) in which accelerated atherogenesis develops.

Material and Methods: Fifty-one female RA patients and 30 female controls were enrolled in the study; 31 of them were without disease-modifying antirheumatic drug (DMARD) treatment and had a relatively short disease duration. Disease activity was assessed by Disease Activity Score (DAS) 28 index. HOMA-IR method was used to detect insulin resistance. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fasting plasma glucose (FPG), insulin, tumor necrosis factor alpha (TNF-α), and IL-18 levels were evaluated. Also, carotid intima-media thickness (cIMT) was measured.

Results: There were no differences between patients and the control group according to age, sex, and body mass index. ESR, CRP, insulin, FPG, HOMA-IR, TNF-α, IL-18 levels, and cIMT measurements were significantly high in the patient group. HOMA-IR and cIMT measurements were similar and high in both the DMARD and non-DMARD patient groups. HOMA-IR correlated with TNF-α (r=0.308, p=0.028), but no correlation was found between IL-18 and HOMA-IR. However, IL-18 was correlated positively with cIMT (r= 0.318, p=0.028) and negatively with BMI (r=-0.360, p=0.01).

Conclusion: IL-18 is associated with atherosclerosis in RA patients. However, no significant relation was found with insulin resistance. IL-18 may be a marker for early evaluation of atherosclerosis in RA patients.