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  plasma creatinine (r=0·7, P = 0·001), antinuclear antibody (ANA) (r= 0.6, p=0.001),
anti double stranded DNA (dsDNA) (r=0.5, p=0.008), ESR1 (r= 0.56, p=0.001). The
concentrations of plasma IL-18 in SLE patients with elevated plasma creatinine were
significantly higher than those with normal plasma creatinine (285.7.6±59.6 pg/ml vs
182.8±29.4, p< 0.001). Also, SLEDAI correlated positively with both plasma levels of
insulin and HOMA-IR values (p<0.05 in both). Conclusions: In SLE patients, a high
IL-18 level reflects activity of the disease and is related to cardiovascular risk factors.
IL-18 is therefore suggested to play a crucial role in triggering the inflammatory
processes of premature atherosclerosis in SLE, in addition to the markers of
disturbed homocysteine metabolism could play a role as mediator of cardiovascular
disorders in SLE.