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Titolo:
Role of TNF-alpha in high-dose antigen therapy in experimental autoimmune neuritis: Inhibition of TNF-alpha by neutralizing antibodies reduces T-cellapoptosis and prevents liver necrosis
Autore:
Weishaupt, A; Gold, R; Hartung, T; Gaupp, S; Wendel, A; Bruck, W; Toyka, KV;
Indirizzi:
Univ Wurzburg, Dept Neurol, Clin Res Grp Multiple Scierosis & Neuroimmunol, D-97080 Wurzburg, Germany Univ Wurzburg Wurzburg Germany D-97080 mmunol, D-97080 Wurzburg, Germany Univ Konstanz, Fac Biol, D-7750 Constance, Germany Univ Konstanz Constance Germany D-7750 c Biol, D-7750 Constance, Germany Free Univ Berlin, Dept Neuropathol, D-1000 Berlin, Germany Free Univ Berlin Berlin Germany D-1000 uropathol, D-1000 Berlin, Germany
Titolo Testata:
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
fascicolo: 5, volume: 59, anno: 2000,
pagine: 368 - 376
SICI:
0022-3069(200005)59:5<368:ROTIHA>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXPERIMENTAL ALLERGIC NEURITIS; CENTRAL-NERVOUS-SYSTEM; LEWIS RAT; MEDIATED DEMYELINATION; ENCEPHALOMYELITIS; RECEPTOR; PROTEIN; LYMPHOCYTES; CYTOKINE; DISEASE;
Keywords:
apoptosis; experimental autoimmune neuritis; immunotherapy; T-lymphocytes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Gold, R Univ Wurzburg, Dept Neurol, Clin Res Grp Multiple Scierosis & Neuroimmunol, Josef Schneider Str 11, D-97080 Wurzburg, Germany Univ Wurzburg Josef Schneider Str 11 Wurzburg Germany D-97080 any
Citazione:
A. Weishaupt et al., "Role of TNF-alpha in high-dose antigen therapy in experimental autoimmune neuritis: Inhibition of TNF-alpha by neutralizing antibodies reduces T-cellapoptosis and prevents liver necrosis", J NE EXP NE, 59(5), 2000, pp. 368-376

Abstract

TNF-alpha has been implicated as a potentially detrimental cytokine in autoimmune disorders of the nervous system and has been reported to be elevated in antigen-specific therapy of experimental autoimmune neuritis (EAN) in vivo. To investigate the role of TNF-alpha in EAN in rats that had been subjected to antigen-specific therapy with human P2 protein, animals were cotreated with an anti-TNF-alpha neutralizing antibody and the effects of the antibody on disease determined. Using this strategy in adoptive transfer (AT-) EAN, antigen-induced T-cell apoptosis in inflamed sciatic nerve and in liver was reduced to levels observed in control animals indicating that TNF-alpha mediates antigen-induced apoptosis of inflammatory T-cells. Focal liver necrosis, which had been observed in earlier studies after antigen therapy in AT-EAN, was prevented by passive immunization with neutralizing anti-TNF-alpha antibody. Unexpectedly, neutralization of TNF-alpha only partly abolished the protective effect of antigen therapy on the overall disease course. This may indicate that inhibition of TNF-alpha exerts beneficial effects other than through T-cell apoptosis, or that some of the benefit of antigen therapy is mediated by other pathways. These results indicate that secretion of TNF-a during antigen therapy has the dual potential to mediate beneficial apoptosis of inflammatory T-cells in the inflammatory lesion and to induce liver damage as a severe side effect.

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Documento generato il 15/07/20 alle ore 21:18:31