Role of Interleukin-18, S-adenosylmethionine and SAdenosylhomocysteine as Cardiovascular Risk Factors in Patients with Systemic Lupus Erythematosus

Abstract

Background:The incidence of Systemic Lupus Erythematosus (SLE) appears to be increasing and the main cause of death in that disease is coronary artery disease since SLE is associated with premature atherosclerosis. The association of plasma interleukin-18 levels and proinflammatory cytokines with cardiovascular risk in SLE patients has not been extensively established. Hyperhomocysteinemia is associated with increased risk for cardiovascular events, but it is not clear whether it is a marker or mediator for vascular dysfunction or a marker for another risk factor. Aim of the work: The purpose of the present study was to determine whether plasma IL-18, SAM, SAH and SAM/SAH ratio are associated with cardiovascular risk factors and disease activity in SLE patients. Subjects and Methods: The plasma concentrations of a novel pro-inflammatory cytokine, interleukin (IL)-18 by ELISA as well as SAM,SAH and SAM/SAH ratio by HPLC was determined in 31 patients with systemic lupus erythematosus (SLE) and 30 sex-and age-matched healthy control subjects and correlated them with cardiovascular risk factors and the SLE disease activity. For every patient the systemic lupus disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Body mass index (BMI), systolic blood pressure, diastolic blood pressure, CBC, liver functions, plasma creatinine, urine analysis, erythrocyte sedimentation rate (ESR)1, ANA, anti-ds DNA, C3, C4, fasting insulin and glucose, plasma lipid profile, plasma SAH,SAM ,SAM/SAH ratio, titers of autoantibodies against oxidized low-density lipoprotein and carotid intima media thickness (CIMT) were determined. SLE patients with a history of diabetes mellitus, hypertension, hyperlipidemia, smoking, or coronary artery disease (CAD) and positive pregnancy test were excluded. Results: The mean age of SLE patients was 35.1±10.3 years and the mean duration of SLE was 4.2± 2.9 years. Plasma concentrations of IL-18 were significantly higher in SLE patients than agematched healthy controls (p< 0.001). Also, plasma SAH is elevated in SLE patients versus controls while SAM and SAM/SAH ratio were significantly lower in SLE patients versus controls. Elevation of plasma IL-18 correlated positively and significantly with SLE disease activity index. In addition, plasma concentrations of IL-18 correlated positively and significantly with BMI, insulin, Homeostasis model assessment insulin resistance (HOMA IR), triglycerides, CIMT, and SAH, in SLE patients. IL18 concentrations showed a positive and significant correlation with