The effect of vesnarinone on TNFα production in human peripheral blood mononuclear cells and microglia: A preclinical study for the treatment of multiple sclerosis

H. Jiang, B. Bielekova, H. Okazaki, K. Clarence-Smith, K. P. Johnson, G. Bergey, R. Martin, S. Dhib-Jalbut

Research output: Contribution to journalArticlepeer-review

Abstract

Vesnarinone (OPC-8212) is a synthetic quinolinone derivative with inotropic and immunomodulatory effects. Vesnarinone has been shown to inhibit tumor necrosis factor-alpha (TNFα) produced by mitogen stimulated macrophages, and to inhibit phosphodiesterase (PDE) type III in cardiac muscle. TNFα and interferon-gamma (IFNγ) have been implicated in the pathogenesis of autoimmune diseases, and both cytokines are targets for therapeutic intervention. IFNγ can enhance autoimmune disease through direct effects, and indirectly by priming macrophages to produce TNFα. In this study, we demonstrate that while vesnarinone enhances basal TNFα levels, it inhibits TNFα production in peripheral blood mononuclear cells from multiple sclerosis (MS) patients and healthy donors stimulated with lipopolysaccharide (LPS) or primed with IFNγ and stimulated with suboptimal doses of LPS. In addition, vesnarinone inhibited TNFα production in primary adult human microglial cultures. However, in contrast to rolipram, another TNFα inhibiting agent, vesnarinone failed to inhibit TNFα production by myelin basic protein specific T-cell lines. As oral TNF inhibitors are currently being considered in the USA for clinical application in MS, the implications of our findings on the development of vesnarinone for treatment of MS are discussed.

Original languageEnglish (US)
Pages (from-to)134-145
Number of pages12
JournalJournal of Neuroimmunology
Volume97
Issue number1-2
DOIs
StatePublished - Jun 1 1999
Externally publishedYes

Keywords

  • IFNγ
  • Microglia
  • Mononuclear cells
  • Multiple sclerosis
  • TNFα
  • Vesnarinone

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'The effect of vesnarinone on TNFα production in human peripheral blood mononuclear cells and microglia: A preclinical study for the treatment of multiple sclerosis'. Together they form a unique fingerprint.

Cite this