In vitro effects of R-verapamil on the cytokine environment and T-lymphocyte proliferation when human T-lymphocyte activation takes place in the presence of acute myelogenous leukemia blasts.

We investigated the effects of R-verapamil on the cytokine environment and T-lymphocyte proliferation when human T-lymphocytes were activated in the presence of accessory cells containing a large population of acute myelogenous leukemia (AML) blasts (nonirradiated blasts for cytokine studies, 50 Gy irradiated blasts in proliferation studies). In the presence of AML blasts, R-verapamil inhibited interleukin 4 (IL4) and interferon-gamma (IFNgamma) release from polyclonal T-cell lines activated with the T-cell mitogen phytohemagglutinin (PHA). R-verapamil also inhibited both the proliferation and the release of IFNgamma and IL10 by normal T-cells stimulated with allogeneic peripheral blood mononuclear cells derived from AML patients. This antiproliferative effect of R-verapamil was seen in the presence of exogenous IL2 but was not observed in the presence of exogenous IL1beta or granulocyte/macrophage colony-stimulating factor GM-CSF). In addition R-verapamil inhibited the release of IL1beta and tumor necrosis factor alpha during allogeneic stimulation.