Elevated production of interleukin-18 is associated with renal disease in patients with systemic lupus erythematosus

To investigate the production mechanism and proinflammatory role of the cytokine interleukin (IL-18) in lupus nephritis, we investigated the plasma concentrations of IL-18 and nitric oxide (NO) and the release of IL-18 and NO from mitogen-activated peripheral blood monomuclear cells (PBMC), in 35 SLE patients with renal disease (RSLE), 37 patients without renal disease (SLE) and 28 sex- and age-matched healthy control subjects (NC). IL-18 and NO concentrations were measured by ELISA and colourimetric non-enzymatic assay, respectively. Gene expressions of IL-18 and IL-18 receptor were analysed by RT-PCR. Plasma IL-18 and NO concentrations were significantly higher in RSLE than NC (both P < 0.01). Elevation of plasma IL-18 in RSLE correlated positively and significantly with SLE -disease activity index and plasma NO concentration (r = 0.623, P < 0.0001 and r = 0.455, P = 0.017, respectively), and the latter also showed a positive and significant correlation with plasma creatinine (r = 0.410, P = 0.034) and urea (r = 0.685, P < 0.0001). There was no significant difference in gene expressions of IL-18 and IL-18 receptor in PBMC among RSLE, SLE and NC. Percentage increase in culture supernatant IL-18 concentration was significantly higher in RSLE than SLE and NC (both P < 0.05). The basal NO release was significantly higher in RSLE than that in SLE and NC (both P < 0.005). IL-18 is therefore suggested to play a crucial role in the inflammatory processes of renal disease in SLE.