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.
Wong
C K
CK
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.
Ho
C Y
CY
Li
E K
EK
Tam
L S
LS
Lam
C W K
CW
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D053727:Interleukin-18 Receptor alpha Subunit; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008181:Lupus Nephritis / Q000175:diagnosis / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D053724:Receptors, Interleukin-18; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D009569:Nitric Oxide