T. Kambayashi et al., VESNARINONE IS A SELECTIVE INHIBITOR OF MACROPHAGE TNF-ALPHA RELEASE, International journal of immunopharmacology, 18(6-7), 1996, pp. 371-378
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