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.
Bruserud
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Section for Hematology, Medical Department B, Haukeland University Hospital, University of Bergen, Norway.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015850:Interleukin-6; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D014700:Verapamil