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

Author： Fushimi T. Inoue A. Koh C.S. Yamazaki M. Ishihara Y. Kim B.S.

ISSN： 0008-8749

Source： Cellular Immunology, Vol.186, Iss.2, 1998-06, pp. : 140-146

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Abstract

Pentoxifylline (PTX) has been recently shown to have a variety of immunomodulatory effects. PTX suppresses the production of tumor necrosis factor-alpha (TNF-alpha) andT helper type 1 (Th1) cytokine, interferon-gamma (IFN-gamma), whereas it increases the production of Th2 cytokines, such as interleukin-4 (IL-4) and IL-10. In the pathogenesis of Theilers 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 SJLJ 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-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; 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-alpha and modulating Th1-dominant immune responses into Th2-dominant ones. Copyright 1998 Academic Press.