Pentoxifylline delays the onset of experimental allergic encephalomyelitis in mice by modulating cytokine production in peripheral blood mononuclear cells.
The effect of pentoxifylline (PTX) on experimental allergic encephalomyelitis (EAE) in mice, a known animal model of multiple sclerosis (MS), was investigated. PTX was orally administrated at 10, 40 and 100 mg/kg/day, respectively. Although oral PTX at these doses had no significant effect on the incidence and severity of EAE, oral PTX (40 mg/kg/day) alone produced a significant delay in the onset of EAE. Semiquantitative reverse transcriptase-polymerase chain reaction analysis revealed that PTX at this dose reduced the mRNA levels for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 in peripheral blood mononuclear cells (PBMC) of mice with EAE. A histopathological study showed that PTX treatment delayed infiltration of inflammatory cells in the central nervous system (CNS) of mice with EAE. These results indicated that the tolerable dose of PTX had a suppressive effect on the induction phase of EAE by modulating cytokine production in PBMC but had no effect on the severity of EAE. The findings in the present study with animals suggested that a tolerable dose of PTX might prolong the intervals between relapses in MS, but might not improve the clinical sign and symptoms of MS.
Okuda
Y
Y
Department of Neurology, Osaka University Medical School, Japan.
Sakoda
S
S
Fujimura
H
H
Yanagihara
T
T
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000517:prevention & control*; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D010431:Pentoxifylline / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D012194:RNA-Directed DNA Polymerase; D010431:Pentoxifylline