S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities . Intracellularly, it exhibits regulatory effects on cell growth, differentiation, cell shape and energy metabolism. Extracellularly, S100B stimulates neuronal survival, differentiation, astrocytic proliferation, neuronal death via apoptosis, and stimulates (in some cases) or inhibits (in others) activity of inflammatory cells.
Several studies suggest that S100B has a role in the pathogenesis of multiple sclerosis (MS). Phenotypically and functionally similar T cells specific against S100B can be detected in the peripheral blood of MS patients making S100B a putative candidate auto-antigen in MS . Furthermore, S100B may act as a cytokine [2, 10, 11] and in vitro studies show that, at high levels, S100 can induce the neuronal expression and secretion of pro-inflammatory interleukin-6. In addition, elevated levels of S100B have been detected in the cerebrospinal fluid (CSF) of MS patients during acute phases or exacerbations of the disease  and it has therefore been proposed that elevated S100B may be indicative of active cell injury .
Interferon-β (IFN-β) is effective in reducing relapse rate in relapsing-remitting [6, 14, 17] and secondary progressive MS  but the mechanisms behind the beneficial action of IFNβ are not fully understood. Two potential sites of action are on cytokine production [1, 4, 12] and on the entry of leukocytes into the CNS [8, 9, 16, 18].
In this clinically negative phase II study , we assessed the effect of IFNβ-1a on serum levels of S100B at 3-month intervals in subjects with primary progressive MS (PPMS). The key questions were whether serum S100B levels correlated with disability or MRI findings in patients with PPMS, and whether IFN-β has an effect on levels of serum S100B.