RECOMBINANT HUMAN INTERLEUKIN-1-BETA INDUCES PRODUCTION OF PROSTAGLANDINS IN PRIMARY HUMAN FETAL ASTROCYTES AND IMMORTALIZED HUMAN FETAL ASTROCYTE CULTURES

Astrocytes play an important role in initiating and modulating inflamm atory responses within the central nervous system. Extensive studies i n rodents have shown that TPA, substance P, calcium ionophore A21387, and lipopolysaccharide (LPS) induce formation and release of arachidon ic acid metabolites which have immunoregulatory properties. To better understand the immunopathology of brain injury, we studied the role of inflammatory cytokines such as tumor necrosis factor alpha, interleuk in (IL) 6, IL-2, interferon gamma and IL-1 beta in the production of a rachidonic acid metabolites in cells from fetal human brain. Among the se cytokines, only IL-1 beta significantly stimulated production of pr ostaglandins E(2) and F-2 alpha but not PGD(2), thromboxane B-2 and 6- keto-PGF(1 alpha). Under our experimental conditions, these astrocyte cultures did not produce metabolites in the lipoxygenase pathway such as leukotrienes B-4 and C-4 upon IL-1 beta stimulation. The stimulator y effects of IL-1 beta on the induction of arachidonic acid metabolite s have been studied in various human cell types but not in astrocytes. Human astrocyte production of PGF(2 alpha) and PGE(2) but not PGD(2), 6-keto-PGF(1 alpha) and TXB(2) when stimulated by IL-1 beta, is thus a novel finding. This observation should initiate investigations into the mechanism of arachidonic acid metabolism and the role of its metab olites in inflammation in the human nervous system.