TNF-α: A Paradigm of Paradox and Complexity in Multiple Sclerosis and its Animal Models~!2009-10-07~!2009-11-23~!2010-07-14~!

TNF-� (tumour necrosis factor-� ) is a pleiotropic cytokine with wide-ranging actions on the immune system and is an important mediator in immune-mediated inflammatory disease states, including multiple sclerosis. TNF-� and its receptors are part of a large and complex superfamily of homologous ligands and receptors, whose many biological func- tions overlap. Investigations have demonstrated the effects of TNF-� at various stages of pathology in multiple sclerosis (MS), including oligodendrocyte death, demyelination, immune cell trafficking, cellular proliferation and major histo- compatibility (MHC) antigen expression. Targeting the TNF-� immunobiological pathway successfully ameliorates dis- ease severity in a number of autoimmune inflammatory conditions except for multiple sclerosis. Anti-TNF-� therapy in experimental autoimmune encephalomyelitis (EAE) showed mixed results, whereas in MS trials it was deleterious. It is clear that TNF-� also has a beneficial role, especially in neuroprotection and regeneration. A clearer understanding of the protective role of TNF-� may be extrapolated from studies in other inflammatory conditions such as stroke and traumatic brain injury.