Association of intercellular adhesion molecule-1 with clinical manifestations and interleukin-18 in patients with active, untreated adult-onset Still's disease

Abstract

To investigate the association of intercellular adhesion molecule 1 (ICAM-1) with clinical manifestations and interleukin-18 (IL-18) levels in patients with active untreated adult-onset Still's disease (AOSD). We determined serum soluble ICAM-1 (sICAM-1) levels by enzyme-linked immunosorbent assay in 50 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls. The levels of ICAM-1 messenger RNA expression in IL-18-stimulated peripheral blood mononuclear cells (PBMCs) and in biopsy specimens obtained from AOSD patients with Still's rash or synovitis were investigated using real-time quantitative polymerase chain reaction. Significantly higher serum levels of sICAM-1 were observed in patients with active untreated AOSD compared with those with active RA and healthy controls. Serum sICAM-1 levels were significantly correlated with the clinical activity score (r = 0.565, P < 0.001), ferritin values (r = 0.462, P < 0.005), and IL-18 levels (r = 0.462, P < 0.005) in patients with AOSD. The serum sICAM-1 level was identified as a predictor of hepatic dysfunction (odds ratio [OR] 1.016, P = 0.011) and disseminated intravascular coagulation (DIC) (OR 1.013, P = 0.023). Up-regulation of ICAM-1 gene expression was demonstrated in IL-18-stimulated PBMCs from patients with AOSD. Increased levels of ICAM-1 transcripts were observed in the biopsy specimens obtained from AOSD patients with Still's rash or synovitis compared with healthy skin and patients with osteoarthritis. The serum sICAM-1 level may be used as a clinical marker to assess disease activity and may predict the occurrence of hepatic dysfunction and DIC in AOSD. IL-18-up-regulated gene expression of ICAM-1 may contribute to the inflammatory response in AOSD.