Increased apoptosis of peripheral blood lymphocytes and its association with interleukin-18 in patients with active untreated adult-onset Still's disease

Abstract

Objective. To determine spontaneous and activation-induced apoptosis of peripheral blood lymphocytes (PBLs) from patients with active untreated adult-onset Still's disease (AOSD) and to examine the role of interleukin-18 (IL-18) involved in the apoptosis related to this disease. Methods. The percentages of spontaneous and IL-18-stimulated apoptotic lymphocytes in peripheral blood of 20 patients with active untreated AOSD, 20 with active untreated systemic lupus erythematosus (SLE), and 20 healthy controls were determined using annexin V/propidium iodide staining and flow cytometry. Serum IL-18 levels were measured using enzyme-linked immunosorbent assay. The transcripts of caspase 3 gene and apoptosis-regulating genes, including Las, FasL, Bcl-2, and p53 in IL-18-treated peripheral blood mononuclear cells (PBMCs) from 8 AOSD patients, 4 SLE patients, and 4 healthy controls, were examined by real-time quantitative polymerase chain reaction. Results. Significantly higher percentages of spontaneous and IL-18-stimulated apoptotic PBLs were found in patients with active untreated AOSD and those with active untreated SLE than in healthy controls. The percentages of spontaneous and IL-18-stimulated apoptotic lymphocytes correlated positively with clinical activity scores and serum IL-18 levels for AOSD patients and SLE patients. The percentages of spontaneous and activation-induced apoptotic PBLs significantly declined, paralleling clinical remission and the decrease in serum IL-18 levels after effective therapj in AOSD patients. Up-regulation of FasL and p53 transcripts was demonstrated in IL-18-treated PBMCs from AOSD patients and SLE patients in a dose-dependent manner. Conclusion. The increased apoptosis of PBLs from AOSD patients may be associated with the effect of IL-18 through up-regulation of FasL and p53 transcripts. © 2007, American College of Rheumatology.