ALTERED APOLIPOPROTEIN-E SECRETION IN CYTOKINE TREATED HUMAN ASTROCYTE CULTURES

Apolipoprotein E (ApoE), postulated to be a major lipid carrier protei n in brain, is synthesized and secreted primarily by astrocytes and is involved in brain development and repair. We have analyzed its secret ion in primary cultures of older (high passage) slowly dividing and yo unger (lower passage) rapidly dividing fetal human astrocytes exposed to various inflammatory and anti-inflammatory cytokines, alone and in combination. ApoE secretion was reduced in high passage astrocytes whe n compared to lower passage astrocytes. A further reduction in ApoE se cretion in high passage cells was consistently produced by the combina tion of cytokines interleukin 1 (Il-1) alpha and beta and interferon ( IFN-gamma) cytokines or by the basic fibroblast growth factor (basic-F GF) alone. Epidermal growth factor (EGF) increased ApoE secretion. The combination of these cytokine effects in chronically degenerating bra in regions of Alzheimer's disease and other neurodegenerative diseases could reduce the amount of ApoE available for neuronal regeneration. EGF, or agents inducing EGF, could ameliorate these ApoE deficiencies. (C) 1997 Elsevier Science B.V.