Increased apoptosis of peripheral blood lymphocytes and its association with interleukin-18 in patients with active untreated adult-onset Still's disease
Article first published online: 29 NOV 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis Care & Research
Volume 57, Issue 8, pages 1530–1538, 15 December 2007
How to Cite
Chen, D.-Y., Hsieh, T.-Y., Hsieh, C.-W., Lin, F.-J. and Lan, J.-L. (2007), Increased apoptosis of peripheral blood lymphocytes and its association with interleukin-18 in patients with active untreated adult-onset Still's disease. Arthritis & Rheumatism, 57: 1530–1538. doi: 10.1002/art.23088
- Issue published online: 29 NOV 2007
- Article first published online: 29 NOV 2007
- Manuscript Accepted: 1 MAY 2007
- Manuscript Received: 12 OCT 2006
- Taichung Veterans General Hospital. Grant Number: TCVGH-923803B
- Apoptosis-regulating genes;
- Adult-onset Still's disease;
- Systemic lupus erythematosus
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.
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.
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.
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.