krn-7000 and Multiple-Sclerosis--Relapsing-Remitting

To extend our studies on glycolipid-reactive invariant Natural Killer T-cell (iNKT-cell) function in multiple sclerosis (MS), we investigated the stimulatory activities of two myelin-derived glycolipids that are poly-acetylated derivatives of β-galactosylceramide designated as fast-migrating cerebrosides (FMC) by thin-layer chromatography. In healthy subjects, FMC stimulation of peripheral blood cells significantly expanded iNKT-cells similar to α-GalCer and induced significant increases in Th1, Th2 and Th17 cytokines. In marked contrast, MS patients failed to respond to FMCs or to α-GalCer stimulation indicating an anergic response. We propose that myelin-derived FMC glycolipids stimulate iNKT-cell responses in vivo and this is blocked in MS.

Topics: Adult; Aged; Carbohydrate Sequence; Cerebrosides; Clonal Anergy; Female; Flow Cytometry; Galactosylceramides; Humans; Male; Middle Aged; Molecular Sequence Data; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Myelin Sheath; Natural Killer T-Cells; Neuroimmunomodulation; Young Adult