Cyclosporin A inhibits cytokine-induced proliferation in B-chronic lymphocytic leukemia

We investigated the effects of the immunosuppressant cyclosporin A (CsA) on proliferation of neoplastic B-cells from patients with B-chronic lymphocytic leukemia (B-CLL). Cell growth was induced in vitro by tumor necrosis factor alpha (TNF-alpha (8/16), interleukin 2 (IL-2 (9/16) or both (7/16), in 4 cases spontaneous proliferation was observed. We were able to demonstrate that CsA inhibits cytokine-induced proliferation, as measured by [3H]-thymidine incorporation, in all cases responsive to TNF-alpha or IL-2 as well as in spontaneous proliferation. CsA did not increase the fraction of trypan blue positive cells or apoptosis. Growth inhibition by CsA occurred in a dose dependent manner: 100 ng/ml CsA was the optimal concentration which blocked about 90% of cytokine induced or spontaneous proliferation. We could also demonstrate that the effect of CsA was reversible and that no blocking effect was observed when CsA was added later than 48 hours after stimulation. Cell cycle analysis using propidium iodide as a DNA stain demonstrated that CsA prohibited the progression of B-CLL cells from the G1-phase to the S-phase of the cell cycle. However, we were also able to show that TNF-alpha induced proliferation of hairy cell leukemia (HCL) was not affected by CsA. This observation indicates that the inhibitory activity of CsA seems to be restricted to only a few haematological diseases such as B-CLL.