Tumor necrosis factor alpha (TNF-α), anti-TNF-α and demyelination revisited: An ongoing story

Tumor necrosis factor alpha (TNF-α) is a cytokine with pleiotropic actions that can be present both as a transmembrane protein and soluble cytokine (sTNF). Both ligands interact with two different receptors, TNFR1 and TNFR2, which mediate their biological effects. TNF-α is involved in the pathogenesis of multiple sclerosis (MS), however, administration of anti-TNF-α agents to MS patients has been associated with increased disease activity. Insomuch as TNFR1 mediates demyelination and TNFR2 remyelination, it could be hypothesized that anti-TNF-α agents which selectively inhibit sTNF or signals from TNFR1 could be effective in treating MS.