Phosphatidylserine suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease.
Intracerebral inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelinating disease. Various cytokines may play an important role in the pathogenesis of this disease. Tumor necrosis factor (TNF)-alpha contributes to the further development of perivascular cellular infiltration and demyelination in the central nervous system (CNS). Phosphatidylserine (PS), a major anionic phospholipid of mammalian cells, has been proposed to function as a regulator of immune and inflammatory responses, especially reducing TNF-alpha production and release in mice. We studied the effect of PS on TMEV-induced demyelinating disease (TMEV-IDD). We injected TMEV intracerebrally into susceptible SJL/J mice and induced TMEV-IDD. PS were injected intraperitonealy, and clinical course and various immunological indicators were closely studied. The results show that when PS were administered in the effector phase. TMEV-IDD was significantly (P < 0.01) suppressed both clinically and histologically. In an ELISPOT assay, the number of TNF-alpha producing spleen cells was low in PS treated mice compared with saline treated control mice. mRNA of TNF-alpha was not detected in spleen cells of mice PS treated in the effector phase. These data suggest that administration of PS suppresses TMEV-IDD by suppressing TNF-alpha production in the effector phase.
Yamazaki
M
M
Department of Medicine (Neurology), Shinshu University School of Medicine, Matsumoto, Japan.
Inoue
A
A
Koh
C S
CS
Sakai
T
T
Ishihara
Y
Y
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D003711:Demyelinating Diseases / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D010718:Phosphatidylserines / Q000494:pharmacology*; D011051:Poliomyelitis / Q000150:complications*; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D017945:Theilovirus / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000914:Antibodies, Viral; D010718:Phosphatidylserines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha