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Inotropic agent vesnarinone inhibits cytokine production and E-selectin expression in human umbilical vein endothelial cells. 1995

Y Sato, and A Matsumori, and S Sasayama
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.

The cytokine modulating effects of inotropic agents on human umbilical vein endothelial cells (HUVEC) were investigated. Confluent HUVEC in 24-well plates were treated with inotropic agents and then stimulated with 10 ng/ml of human interleukin (IL)-1 beta. After 24 h of incubation, the cytokine levels in the culture supernatants were determined by specific enzyme-linked immunosorbent assay (ELISA) kits. Vesnarinone [OPC-8212; 3,4-dihydro-6-(4-(3,4-dimethoxybenzoil)-1-piperazinyl)-2(1H)- quinolinone] at 26 mumol/l significantly suppressed the production of IL-6, granulocyte macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) induced by IL-1 beta. Although 8 bromoadenosine 3'5' cyclic monophosphate (8Br-cAMP) at 100 mumol/l also inhibited the production of these cytokines, the inhibitory effect was less marked than that of vesnarinone. Amrinone at 26 mumol/l and NKH477 at 10 nmol/l also had a less marked inhibitory effect against the production of IL-6. Next, the inhibitory effect of inotropic agents against the expression of the adhesion molecules of HUVEC was measured by a cell ELISA method. Vesnarinone at 26 mumol/l and NKH477 at 10 mumol/l, a water soluble forskolin derivative used as a positive control, both significantly inhibited the expression of E-selectin induced by 10 ng/ml of human tumor necrosis factor (TNF)-alpha. Amrinone at 26 mumol/l did not inhibit the expression of E-selectin. The level of HUVEC cAMP induced by vesnarinone at 26 mumol/l was much lower than that induced by NKH477 at 10 mumol/l. Moreover, according to a 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay, vesnarinone did not affect the viability of HUVEC. The immunosuppressive effects of vesnarinone described above are not derived from either a cAMP elevating effect or a cytotoxic effect against HUVEC. Although the cytokine network in heart failure has not yet been elucidated, patients with congestive heart failure might benefit from the immunomodulating effects of inotropic agents.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D009503 Neutropenia A decrease in the number of NEUTROPHILS found in the blood. Neutropenias
D011719 Pyrazines A heterocyclic aromatic organic compound with the chemical formula C4H4N2. Pyrazine
D011804 Quinolines
D002316 Cardiotonic Agents Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE). Cardiac Stimulant,Cardiac Stimulants,Cardioprotective Agent,Cardioprotective Agents,Cardiotonic,Cardiotonic Agent,Cardiotonic Drug,Inotropic Agents, Positive Cardiac,Myocardial Stimulant,Myocardial Stimulants,Cardiotonic Drugs,Cardiotonics,Agent, Cardioprotective,Agent, Cardiotonic,Drug, Cardiotonic,Stimulant, Cardiac,Stimulant, Myocardial
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003864 Depression, Chemical The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Depression,Chemical Depressions,Depressions, Chemical
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums

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