Role of TNF-α in high-dose antigen therapy in experimental autoimmune neuritis: Inhibition of TNF-α by neutralizing antibodies reduces T-cell apoptosis and prevents liver necrosis

Andreas Weishaupt, Ralf Gold, Thomas Hartung, Stefanie Gaupp, Albrecht Wendel, Wolfgang Brück, Klaus V. Toyka

Research output: Contribution to journalArticle

Abstract

TNF-α 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-α in EAN in rats that had been subjected to antigen-specific therapy with human P2 protein, animals were cotreated with an anti-TNF-α 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- α 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-α antibody. Unexpectedly, neutralization of TNF-α only partly abolished the protective effect of antigen therapy on the overall disease course. This may indicate that inhibition of TNF-α 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-α 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.

Original languageEnglish (US)
Pages (from-to)368-376
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume59
Issue number5
StatePublished - May 2000
Externally publishedYes

Fingerprint

Experimental Autoimmune Neuritis
Neutralizing Antibodies
Necrosis
Apoptosis
T-Lymphocytes
Antigens
Liver
Adoptive Transfer
Therapeutics
Autoimmune Diseases of the Nervous System
Passive Immunization
Sciatic Nerve
Anti-Idiotypic Antibodies
Cytokines

Keywords

  • Apoptosis
  • Experimental autoimmune neuritis
  • Immunotherapy
  • T-lymphocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Role of TNF-α in high-dose antigen therapy in experimental autoimmune neuritis : Inhibition of TNF-α by neutralizing antibodies reduces T-cell apoptosis and prevents liver necrosis. / Weishaupt, Andreas; Gold, Ralf; Hartung, Thomas; Gaupp, Stefanie; Wendel, Albrecht; Brück, Wolfgang; Toyka, Klaus V.

In: Journal of Neuropathology and Experimental Neurology, Vol. 59, No. 5, 05.2000, p. 368-376.

Research output: Contribution to journalArticle

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