VESNARINONE IS A SELECTIVE INHIBITOR OF MACROPHAGE TNF-ALPHA RELEASE

Vesnarinone is an experimental drug that has been used successfully in the treatment of congestive heart failure patients. In this report we investigate the effect of vesnarinone on the cytokine secretory produ cts of mononuclear phagocytes. In a concentration-dependent manner, th e drug inhibits the endotoxin(LPS)stimulated release of tumor necrosis factor (TNF)alpha and suppresses interleukin(IL)-6 release, but does not affect the release of IL-1 alpha, IL-10 and leukemia inhibitory fa ctor (LIF) by mouse peritoneal macrophages. Using competitive polymera se chain reaction (PCR) analyses, we find that vesnarinone significant ly reduces TNF alpha, but not IL-10 mRNA. In addition to LPS, the drug inhibits TNF alpha release induced by several other stimuli. The inhi bitory effect of the drug on the TNF alpha biosynthesis can be observe d in differentiated human monocytes, in macrophage cell lines, and in synovial adherent cells from rheumatoid arthritis patients. Although t he precise mode of action of vesnarinone in the signal transduction pa thway leading to the selective inhibition of TNF alpha is not known, t he drug might be useful in the treatment of diseases involving that cy tokine. Copyright (C) 1996 International Society for Immunopharmacolog y