Anti-TNF therapy abrogates autoimmune demyelination

Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461.
Annals of Neurology (Impact Factor: 9.98). 11/1991; 30(5):694-700. DOI: 10.1002/ana.410300510
Source: PubMed


To define a role for the cytokine tumor necrosis factor (TNF) in immune-mediated demyelination, the effect of anti-TNF antibody was investigated with a form of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice induced by the adoptive transfer of myelin basic protein-(MBP)-sensitized T lymphocytes, an animal model of the human disease multiple sclerosis (MS). In three separate experiments, no mouse sensitized for EAE and then treated with anti-TNF by intraperitoneal injection developed signs of central nervous system (CNS) disease. Examination of CNS tissue from anti-TNF-treated animals showed no pathological changes. CNS tissue from control animals demonstrated extensive inflammatory cell infiltration and demyelination. To test whether anti-TNF therapy was inhibitory to encephalitogenic cells, preincubation of MBP-sensitized T lymphocytes with anti-TNF in vitro prior to injection into recipient mice was performed, and resulted in no diminution of their ability to transfer EAE. In addition, spleen cells from anti-TNF-treated mice were capable of serial transfer of EAE, similar to spleen cells from control animals. However, spleen cells from anti-TNF-treated mice did not produce TNF on stimulation with MBP or concanavalin A. This study showed that anti-TNF antibody can inhibit effectively the development of EAE by interfering with the effector, rather than the induction, phase of the disease. Anticytokine therapy may have important applications in the development of new therapeutic strategies for MS.

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    • "An example in MS is a monoclonal antibody (mAb) against the inflammatory cytokine TNF-α, which is a highly successful treatment in rheumatoid arthritis and the EAE model (Selmaj et al., 1991 "
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    European journal of pharmacology 05/2015; 759:14-8. DOI:10.1016/j.ejphar.2015.03.030 · 2.53 Impact Factor
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    • "The role of TNF-α in the pathogenesis of inflammatory demyelinating disease of the central nervous system has been demonstrated in rodents [54] and in humans [55-57]. Transgenic mice that constitutively express TNF-α in the CNS can trigger the development of a chronic inflammatory demyelinating disease [58]. "
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    PLoS ONE 12/2013; 8(12):e83119. DOI:10.1371/journal.pone.0083119 · 3.23 Impact Factor
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    • "The role of TNF-α in the pathogenesis of CNS autoimmunity is unclear. In studies utilizing the murine MS model, EAE, both TNF-α- and TNFR1-deficient mice are resistant to disease and the use of anti-TNF or sTNF receptor antibodies reduced disease severity [17, 46, 47]. In addition, transgenic mice that over-express TNF-α spontaneously develop chronic, inflammatory demyelinating disease [45]. "
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