Suppressive effects of TNF-alpha on myelin formation in vitro.

Using organotypic cultures of ICR mouse cerebellum, we studied the effects of TNF-alpha on myelin formation, and its demyelinating effects. Mature, myelinated cultures were resistant to TNF-alpha, even at the highest concentration examined, 1 x 10(4) U/ml. However, when cultures were grown in medium containing TNF-alpha from the time of explantation, myelin formation was significantly affected at a concentration of 1 x 10(2) U/ml. The myelin sheaths formed were very thin, partial, and few in number. When TNF-alpha was removed from the medium within 6 days, myelin formation was recovered. Although our in vitro system tests factors that influence myelin formation but not remyelination, these results suggest that TNF-alpha may be involved in the remyelination block following acute myelin breakdown.