Release of Cytokines from Human Umbilical Vein Endothelial Cells Treated with Platinum Compounds in vitro

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Abstract
Endothelial cells (EC) produce cytokines, such as interleukin (IL)‐1, IL‐6, IL‐8 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). These cytokines have an important role in the proliferation and differentiation of hematopoietic progenitor cells. On the other hand, anticancer agents generally cause hematopoietic disorders. However, little is known about the effects of chemotherapeutic agents on the secretion of cytokines from EC. Therefore, we investigated if treatment with platinum compounds may stimulate EC to secrete cytokines. EC newly isolated from a human umbilical vein were exposed to cisplatin, carboplatin, or TRK‐710 for 80 min, then the cells were washed and placed in fresh medium. The levels of cytokines in the fresh medium were measured by the ELISA method, the levels of intracellular hydrogen peroxide (H2O2) were measured by flow cytometry, and the rhodamine 123‐stained live mitochondria of the EC were observed under a confocal laser microscope. Platinum compounds induced cytokine production in human EC: cisplatin most prominently induced the release of IL‐1 and IL‐6, and TRK‐710 had the greatest ability to induce the release of GM‐CSF. Intracellular H2O2 production and IL‐8 release were transiently induced immediately after treatment with platinum compounds, leading to IL‐1 release when H2O2 production was eliminated. These results may provide new insights into the hematological toxicity induced by anticancer agents and the role of IL‐1 and IL‐6 secreted from EC in this toxicity.