The effect of pentoxifylline (PTX) on Theiler's murine encephalomyelitis (TMEV)-induced demyelinating disease.
Pentoxifylline (PTX) has been recently shown to have a variety of immunomodulatory effects. PTX suppresses the production of tumor necrosis factor-alpha (TNF-alpha) and T 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 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-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.
Department of Medicine (Neurology), Shinshu University School of Medicine, Matsumoto, Japan.
T
T
Fushimi
A
A
Inoue
C S
CS
Koh
M
M
Yamazaki
Y
Y
Ishihara
B S
BS
Kim
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D002455:Cell Division; D002460:Cell Line; D006224:Cricetinae; D016207:Cytokines / Q000097:blood; D003711:Demyelinating Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D051379:Mice; D010431:Pentoxifylline / Q000627:therapeutic use*; D011051:Poliomyelitis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D017945:Theilovirus; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000914:Antibodies, Viral; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D010431:Pentoxifylline