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 P P