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


CONCLUSIONS
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.
Chen
Der-Yuan
DY
National Yang-Ming University, Taipei, Taiwan.
Hsieh
Tsu-Yi
TY
Hsieh
Chia-Wei
CW
Lin
Fang-Ju
FJ
Lan
Joung-Liang
JL
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000097:blood* / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016706:Still's Disease, Adult-Onset / Q000097:blood* / Q000209:etiology / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D020382:Interleukin-18; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3