A GLIOTOXIC FACTOR AND MULTIPLE-SCLEROSIS

The pathogenesis of multiple sclerosis (MS) is unknown. Searching for possible toxic factors, it was found that 3-day exposure to heat-treat ed cerebrospinal fluid (CSF) from MS patients caused apoptotic death o f astrocytes and oligodendrocytes, but not fibroblasts, myoblasts, Sch wann cells, endothelial cells and neurons, in vitro. CSFs from other i nflammatory or non-inflammatory neurological diseases showed no toxici ty. Exposure of these glial cells to partially purified MS CSF produce d DNA fragmentation, apoptotic bodies, chromatin condensation, cell sh rinkage, and changes in the levels of known cytokines. A cytotoxic fac tor, called gliotoxin, was characterized chromatographically as a stab le 17-kDa glycoprotein. Since this protein is highly cytotoxic for ast rocytes and oligodendrocytes, it may represent an initial pathogenic f actor, leading to the neuropathological features of MS, such as blood- brain barrier involvement and demyelination. (C) 1998 Elsevier Science B.V.