Active untreated adult-onset Still's disease & the Role of Interluekin-18

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Still's Disease: Increased apoptosis of peripheral blood lymphocytes and its

association with interleukin-18 in patients with active untreated

adult-onset Still's disease

http://www3.interscience.wiley.com/cgi-bin/abstract/117347103/ABSTRACT

Arthritis Care & Research

Volume 57, Issue 8 , Pages 1530 - 1538

Copyright © 2007 by the American College of Rheumatology

*Correspondence to Joung-Liang Lan, Department of Internal Medicine,

Taichung Veterans General Hospital, No. 160, Section 3, Taichung-Kang Road,

Taichung City, 40705, Taiwan

email: Joung-Liang Lan (jllan@...)

Funded by: Taichung Veterans General Hospital; Grant Number: TCVGH-923803B

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.