DISTINCT EXPRESSIONS OF 3 CYTOKINES BY IL-1-STIMULATED ASTROCYTES IN-VITRO AND IN AIDS BRAIN

Interleukin-1 (n-1) is elevated in brain tissue of individuals who die d with acquired immunodeficiency syndrome (AIDS) and other diseases wh ere this cytokine likely stimulates reactive astrocytosis. IL-1 stimul ates, among others, production of interleukin-6 (IL-6), granulocyte ma crophage colony-stimulating factor (GM-CSF), and tumor necrosis factor -alpha (TNF-alpha) in cultured astrocytes and astrocytoma cell lines. These and other cytokines may contribute to the neuropathogenesis afte r infection by human immunodeficiency virus type-1 (HIV-1). For exampl e, concentration of TNF-alpha is increased in brain tissue of individu als who died with AIDS and correlates with the severity of AIDS Dement ia Complex (ADC). TNF-alpha and IL-6 have been immunocytochemically de tected in brain tissue but they have not been localized to astrocytes. We, therefore, examined the expression of IL-6, GM-CSF, and TNF-alpha in human primary astrocytes and astrocytoma cell lines U251 and 253 e xposed to IL-1 in serum-free medium. In addition, we immunocytochemica lly assayed GM-CSF expression by astrocytes in brain tissue (n = 8). T he three cytokines were differentially induced in cultured astrocytes by IL-1. The astrocytoma cell lines recapitulated cytokine-specific pa tterns of expression in astrocytes. The patterns were characterized by amounts produced, compartmentalization (intra- and/or extracellular), time courses, and optimal doses of IL-1 for induction. GM-SCF-like im munoreactivity was detected in some but not all, GFAP(+) cells. GM-CSF +/GFAP(+) cells were detected in only three of seven cases containing GM-CSF immunoreactivity. Thus, a discrepancy may exist between human a strocytic cytokine expression in vitro and in tissue. Novel methods th erefore may need to be developed to recapitulate in vitro the heteroge neity of astrocytic cytokine expression in AIDS and other brain tissue . (C) 1995 Academic Press, Inc.