PMID- 10408967
OWN - NLM
STAT- MEDLINE
DCOM- 19990712
LR  - 20201209
IS  - 0165-5728 (Print)
IS  - 0165-5728 (Linking)
VI  - 97
IP  - 1-2
DP  - 1999 Jun 1
TI  - The effect of vesnarinone on TNF alpha production in human peripheral blood 
      mononuclear cells and microglia: a preclinical study for the treatment of 
      multiple sclerosis.
PG  - 134-45
AB  - Vesnarinone (OPC-8212) is a synthetic quinolinone derivative with inotropic and 
      immunomodulatory effects. Vesnarinone has been shown to inhibit tumor necrosis 
      factor-alpha (TNF alpha) produced by mitogen stimulated macrophages, and to 
      inhibit phosphodiesterase (PDE) type III in cardiac muscle. TNF alpha and 
      interferon-gamma (IFNgamma) have been implicated in the pathogenesis of 
      autoimmune diseases, and both cytokines are targets for therapeutic intervention. 
      IFNgamma can enhance autoimmune disease through direct effects, and indirectly by 
      priming macrophages to produce TNF alpha. In this study, we demonstrate that 
      while vesnarinone enhances basal TNF alpha levels, it inhibits TNF alpha 
      production in peripheral blood mononuclear cells from multiple sclerosis (MS) 
      patients and healthy donors stimulated with lipopolysaccharide (LPS) or primed 
      with IFNgamma and stimulated with suboptimal doses of LPS. In addition, 
      vesnarinone inhibited TNF alpha production in primary adult human microglial 
      cultures. However, in contrast to rolipram, another TNF alpha inhibiting agent, 
      vesnarinone failed to inhibit TNF alpha 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.
FAU - Jiang, H
AU  - Jiang H
AD  - Department of Neurology, University of Maryland at Baltimore, 21201, USA.
FAU - Bielekova, B
AU  - Bielekova B
FAU - Okazaki, H
AU  - Okazaki H
FAU - Clarence-Smith, K
AU  - Clarence-Smith K
FAU - Johnson, K P
AU  - Johnson KP
FAU - Bergey, G
AU  - Bergey G
FAU - Martin, R
AU  - Martin R
FAU - Dhib-Jalbut, S
AU  - Dhib-Jalbut S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antigens, Viral)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Pyrazines)
RN  - 0 (Pyrrolidinones)
RN  - 0 (Quinolines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 5COW40EV8M (vesnarinone)
RN  - 82115-62-6 (Interferon-gamma)
RN  - K676NL63N7 (Rolipram)
SB  - IM
MH  - Adjuvants, Immunologic/*pharmacology
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Antigens, Viral/immunology
MH  - Cell Division/drug effects/immunology
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Influenza, Human/immunology
MH  - Interferon-gamma/biosynthesis
MH  - Lipopolysaccharides/pharmacology
MH  - Microglia/cytology/drug effects/*metabolism
MH  - Multiple Sclerosis/*drug therapy/immunology/metabolism
MH  - Pyrazines
MH  - Pyrrolidinones/pharmacology
MH  - Quinolines/*pharmacology
MH  - Rolipram
MH  - T-Lymphocytes/cytology/*metabolism/virology
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
EDAT- 1999/07/17 10:00
MHDA- 2000/06/01 09:00
CRDT- 1999/07/17 10:00
PHST- 1999/07/17 10:00 [pubmed]
PHST- 2000/06/01 09:00 [medline]
PHST- 1999/07/17 10:00 [entrez]
AID - S0165-5728(99)00037-5 [pii]
AID - 10.1016/s0165-5728(99)00037-5 [doi]
PST - ppublish
SO  - J Neuroimmunol. 1999 Jun 1;97(1-2):134-45. doi: 10.1016/s0165-5728(99)00037-5.