The Effect of Pentoxifylline (PTX) on Theiler's Murine Encephalomyelitis Virus (TMEV)-Induced Demyelinating Disease

Abstract

Pentoxifylline (PTX) has been recently shown to have a variety of immunomodulatory effects. PTX suppresses the production of tumor necrosis factor-α (TNF-α) andT helper type 1 (Th1) cytokine, interferon-γ (IFN-γ), whereas it increases the production of Th2 cytokines, such as interleukin-4 (IL-4) and IL-10. In the pathogenesis of Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD), encephalitogenic Th1 cells may play a major role. We examined the effect of PTX treatment on TMEV-IDD. We treated SJL/J mice, inoculated TMEV intracerebrally, with either PTX or saline from days −2 to 12 and days 14 to 27 postintracerebral infection. In the group of mice treated with PTX from days −2 to 12, the onset of TMEV-IDD was suppressed. On the other hand, in the group of mice treated with PTX from days 14 to 27 or saline, the onset of TMEV-IDD was not inhibited. The results of enzyme-linked immunospot (ELISPOT) assay of spleen cells of mice showed that the production of TNF-α and IFN-γ was significantly inhibited (TNF-α and IFN-γ,P< 0.001) and IL-4 and IL-10 production was significantly increased (IL-4,P< 0.001; and IL-10,P< 0.05, respectively) in the group of mice treated with PTX from days −2 to 12. These findings suggest that PTX suppresses the onset of TMEV-IDD by suppressing the production of TNF-α and modulating Th1-dominant immune responses into Th2-dominant ones.