RELEASE OF CYTOKINES FROM HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS TREATED WITH PLATINUM COMPOUNDS IN-VITRO

Endothelial cells (EC) produce cytokines, such as interleukin (IL)-1, IL-6, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CS F), These cytokines have an important role in the proliferation and di fferentiation of hematopoietic progenitor cells. On the other hand, an ticancer agents generally cause hematopoietic disorders, However, litt le is known about the effects of chemotherapeutic agents on the secret ion of cytokines from EC, Therefore, we investigated if treatment with platinum compounds may stimulate EC to secrete cytokines. EC newly is olated from a human umbilical vein were exposed to cisplatin, carbopla tin, or TRK-710 for 80 min, then the cells were washed and placed in f resh medium, The levels of cytokines in the fresh medium were measured by the ELISA method, the levels of intracellular hydrogen peroxide (H 2O2) were measured by flow cytometry, and the rhodamine 123-stained li ve mitochondria of the EC were observed under a confocal laser microsc ope. Platinum compounds induced cytokine production in human EC: cispl atin most prominently induced the release of IL-1 and IL-6, and TRK-71 0 had the greatest ability to induce the release of GM-CSF. Intracellu lar H2O2 production and IL-8 release were transiently induced immediat ely after treatment with platinum compounds, leading to IL-1 release w hen H2O2 production was eliminated. These results may provide new insi ghts into the hematological toxicity induced by anticancer agents and the role of IL-1 and IL-6 secreted from EC in this toxicity.