Cytokine regulation of apoptosis and Bcl-2 expression in lymphocytes of patients with systemic lupus erythematosus.
Both faulty regulation of apoptosis and the inappropriate expression of several interleukins have been considered important defects of lymphocytes in the human autoimmune disease systemic lupus erythematosus (SLE). We therefore tested the in vitro effect of recombinant interleukin (IL-)-2, 4, 7, and 15 on peripheral blood mononuclear cells from patients with SLE and from healthy volunteers. Intracellular Bcl-2 and Bax expression was measured by fluorocytometry and the rate of apoptosis was determined by the TUNEL technique and propidium iodide staining. IL-2, IL-4, IL-7 and IL-15 led to a significant increase in Bcl-2 and a reduction in cell death rates, which was even more pronounced in SLE. Bax levels remained unchanged. Interestingly, the high ex vivo Bcl-2 content of lymphocytes from some SLE patients was maintained after growth factor withdrawal. Anti-apoptotic cytokine signaling may significantly influence the deregulation of cell death in SLE lymphocytes.
Graninger
W B
WB
Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Austria.
Steiner
C W
CW
Graninger
M T
MT
Aringer
M
M
Smolen
J S
JS
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000276:immunology
D016207:Cytokines; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D015847:Interleukin-4