Release of interleukin-6 in cultured B-chronic lymphocytic leukaemia cells is associated with both activation and cell death via apoptosis.
BACKGROUND
There is growing evidence that some cytokines promote B cell survival, while others enhance cell death. Interleukin-6 was reported to induce proliferation of chronic lymphocytic leukaemia (B-CLL) cells, and to enhance survival of these cells through inhibition of spontaneous apoptosis.


METHODS
To more clearly define the effects of an in vitro stimulation of B-CLL cells, lymphocytes from 13 patients with B-CLL and from 6 healthy individuals were incubated for 7 d with immunomodulators such as interleukin-6 (IL-6), pokeweed mitogen (PWM), lipopolysaccharides (LPS), and extracts from Viscum album L. (VAL; Helixor), which were recognised to induce apoptosis but also to induce a release of pro-inflammatory cytokines such as IL-1, IL-6, and tumour necrosis factor-alpha.


RESULTS
Although both, IL-6 and PWM induced a release of IL-6 and expression of the activation markers CD25 and CD71 on the surface of B-CLL cells, IL-6 did not increase or accelerate the proliferation of these cells. In contrast, VAL extracts did not result in an upregulation of activation markers or proliferation of B-CLL cells but induced both, cell death via apoptosis and IL-6 release. In response to PWM, only few clones of leukemic B cells incorporated the thymidine-analogue 5-bromo-2'-deoxyuridine. Moreover, a remarkable response of B-CLL cells towards the immunomodulators was observed only in one patient with an advanced stage.


CONCLUSIONS
These preliminary results do not support theoretical objections of a B-CLL stimulation via induction of IL-6 in vitro.
Büssing
A
A
Krebsforschung Herdecke, Department of Applied Immunology, University Witten Herdecke, Germany. ArBuess@t-online.de
Stein
G M
GM
Stumpf
C
C
Schietzel
M
M
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D015850:Interleukin-6; D001973:Bromodeoxyuridine