Release of interleukin-6 in cultured B-chronic lymphocytic leukaemia cellsis associated with both activation and cell death via apoptosis

Background: There is growing evidence that some cytokines promote B cell su rvival, while others enhance cell death. Interleukin-6 was reported to indu ce proliferation of chronic lymphocytic leukaemia (B-CLL) cells, and to enh ance survival of these cells through inhibition of spontaneous apoptosis. M aterials and Methods: To more clearly define the effects of an in vitro sti mulation 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 i nterleukin-6 (IL-6), pokeweed mitogen (PWM), lipopolysaccharides (LPS), and extracts from Viscum album L. (VAL; Helixor(R), which were recognised to i nduce apoptosis but also to induce a release of pro-inflammatory cytokines such as IL-1, IL-6, and tumour necrosis factor-alpha. Results: Although bot h, 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 d id 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 thym idine-analogue 5-bromo-2'-deoxyuridine. Moreover, a remarkable response of B-CLL cells towards the immunomodulators was observed only in one patient w ith an advanced stage. Conclusions: These preliminary results do not suppor t theoretical objections of a B-CLL stimulation via induction of IL-6 in vi tro.