CYCLOSPORINE-A INHIBITS CYTOKINE-INDUCED PROLIFERATION IN B-CHRONIC LYMPHOCYTIC-LEUKEMIA

We investigated the effects of the immunosuppressant cyclosporin A (Cs A) on proliferation of neoplastic B-cells from patients with B-chronic lymphocytic leukemia (B-CLL). Cell growth was induced in vitro by tum or necrosis factor alpha (TNF-alpha (8/16), interleukin 2 (IL-2 (9/16) or bath (7/16), in 4 cases spontaneous proliferation was observed. We were able to demonstrate that CsA inhibits cytokine-induced prolifera tion, as measured by [H-3]-thymidine incorporation, in all cases respo nsive to TNF-alpha or IL-2 as well as in spontaneous proliferation. Cs A did not increase the fraction of trypan blue positive cells or apopt osis. Growth inhibition by CsA occurred in a dose dependent manner: 10 0 ng/ml CsA was the optimal concentration which blocked about 90% of c ytokine induced or spontaneous proliferation. We could also demonstrat e that the effect of CsA was reversible and that no blocking effect wa s observed when CsA was added later than 48 hours after stimulation. C ell cycle analysis using propidium iodide as a DNA stain demonstrated that CsA prohibited the progression of B-CLL cells from the G(1)-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 ac tivity of CsA seems to be restricted to only a few haematological dise ases such as B-CLL.