Propentofylline inhibits production of TNFalpha and infection of LP-BM5 murine leukemia virus in glial cells.
We examined the effects of a xanthine derivative, propentofylline, on TNFalpha production by glial cells and on infection ofglial cells with a murine leukemia virus, LP-BM5, which induces murine AIDS in susceptible mice. Propentofylline suppressed TNFalpha production in glial cells and also effectively suppressed infection ofglial cells with LP-BM5 in vitro. Addition ofTNFalpha, but not IL-1 or IL-6, abolished the suppressive effects ofpropentofylline. Anti-TNFalpha antibody also suppressed infection of LP-BM5 in these cells. These findings suggest that propentofylline suppressed LP-BM5 infection in glial cells by suppressing TNFalpha production by these cells. Because propentofylline reportedly passes through the blood-brain barrier, it may be useful in the treatment of central nervous system involvement by HIV infection or neurological diseases in which TNFalpha plays a causative role, such as multiple sclerosis.
Suzumura
A
A
Department of Neurology, Nara Medical University, Shijocho, Kashihara, Japan.
Sawada
M
M
Makino
M
M
Takayanagi
T
T
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016679:Genome, Viral; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000187:drug effects* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology* / Q000627:therapeutic use
D000906:Antibodies; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014970:Xanthines; C032114:propentofylline; D010431:Pentoxifylline