Effects of vesnarinone on cytokine production and activation of murine microglia

Tumor necrosis factor alpha (TNF alpha) is considered to play a critical role in the development of various pathological processes in the central nervous system (CNS), such as neuronal degeneration, demyelination and gliosis. In order to search for agents which suppress TNF alpha production in the CNS for future treatment of these pathological conditions, the effects of a synthetic oral inotropic agent, vesnarinone, on murine microglia were examined. Vesnarinone significantly suppressed TNF alpha production by microglia in a dose-dependent manner, without affecting their viability, enzyme activity or expression of the major histocompatibility complex. Since the reported maximum serum concentration is high enough to suppress TNF alpha production in vitro (about 20 microM) after oral administration of the therapeutic dose of vesnarinone, this drug will be useful to treat intractable neurological diseases such as neurodegenerative disorders, multiple sclerosis or HIV-related neurological disorders.