OBJECTIVE:. To examine the hypothesis that patients with systemic lupus erythematosus (SLE) have increased concentrations of interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) and that these cytokines are associated with coronary risk factors and atherosclerosis. Plasma IL-6, MCP-1, and serum IL-8 (pg/ml) concentrations were measured in 74 patients with SLE and in 85 controls. Clinical characteristics, homocysteine, lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and coronary artery calcification as detected by electron beam computed tomography were measured. IL-6 (13.2 +/- 13.8 pg/ml vs 6.7 +/- 3.2 pg/ml, p < 0.001) and MCP-1 (264.2 +/- 581.8 pg/ml vs 131.0 +/- 63.7 pg/ml, p < 0.001) concentrations were higher in patients with lupus than in controls. IL-8 concentrations did not differ between patients and controls (p = 0.86). In patients, IL-6 concentrations were correlated with CRP (p < 0.001), ESR (p < 0.001), SLE disease activity index (SLEDAI, p = 0.003), and body mass index (BMI, p = 0.003). IL-6 concentrations were inversely correlated with HDL cholesterol (p = 0.01). MCP-1 concentrations were correlated with SLEDAI (p = 0.01), ESR (p = 0.04), and triglycerides (p = 0.03). After controlling for age, sex, disease activity, SLICC damage index, smoking status, and systolic blood pressure, IL-6 was associated with coronary calcification (odds ratio, OR = 1.07, p = 0.035). Similar models found no association between MCP-1 or IL-8 with coronary artery calcification. Patients with SLE have increased concentrations of IL-6 and MCP-1. These cytokines are associated with increased inflammation, BMI, and adverse lipid profiles. IL-6 is associated with burden of atherosclerosis in SLE.