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 Fas, 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 therapy 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.