THE EFFECT OF PENTOXIFYLLINE (PTX) ON THEILERS MURINE ENCEPHALOMYELITIS VIRUS (TMEV)-INDUCED DEMYELINATING DISEASE

Pentoxifylline (PTX) has been recently shown to have a variety of immu nomodulatory effects. PTX suppresses the production of tumor necrosis factor-alpha (TNF-alpha) and T helper type 1 (Th1) cytokine, interfero n-gamma (IFN-gamma), whereas it increases the production of Th2 cytoki nes, such as interleukin-4 (IL-4) and IL-10. In the pathogenesis of Th eiler's murine encephalomyelitis virus (TMEV)-induced demyelinating di sease (TMEV-IDD), encephalitogenic Th1 cells may play a major role. We examined the effect of PTX treatment on TMEV-IDD. We treated SJL/J mi ce, inoculated TMEV intracerebrally, with either PTX or saline from da ys -2 to 12 and days 14 to 27 postintracerebral infection. In the grou p of mice treated with PTX from days -2 to 12, the onset of TMEV-IDD w as suppressed. On the other hand, in the group of mice treated with PT X from days 14 to 27 or saline, the onset of TMEV-IDD was not inhibite d. The results of enzyme-linked immunospot (ELISPOT) assay of spleen c ells of mice showed that the production of TNF-alpha and IFN-gamma was significantly inhibited (TNF-alpha and IFN-gamma, P < 0.001) and IL-4 and IL-10 production was significantly increased (IL-4, P < 0.001; an d 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 on set of TMEV-IDD by suppressing the production of TNF-alpha and modulat ing Th1-dominant immune responses into Th2-dominant ones. (C) 1998 Aca demic Press.