Cultures of astrocytes and microglia express interleukin 18

Interleukin 18 (IL-18 or interferon-gamma inducing factor) is a recently di scovered pro-inflammatory cytokine and powerful stimulator of the cell-medi ated immune response. IL-18 is produced by several sources including monocy tes/macrophages, keratinocytes and the zona reticularis and zona fasciculat a of the adrenal cortex. IL-18 occurs in brain but its cellular source in t he CNS has never been investigated. The presence of IL-18 and its response to stimulation in the brain was tested with primary cultures of microglia, astrocytes and hippocampal neurons. IL-18 mRNA was present in astrocytes an d microglia, but not in neurons. The endotoxin lipopolysaccharide (LPS) did not affect IL-18 in astrocytes, but LPS robustly increased IL-18 mRNA in m icroglia. IL-18 protein was constitutively expressed in astrocytes and indu ced in microglia by LPS. The levels of interleukin-1 beta converting enzyme (ICE), an activating enzyme, and caspase 3 (CPP32), an inactivating enzyme , were assessed to investigate the presence of the appropriate processing e nzymes in the cultured cells. ICE was present at constitutive levels in mic roglia and astrocytes suggesting that these cell types may produce and secr ete matured IL-18. Active forms of CPP32 were not detectable in either cell type indicating the absence of a degradative pathway of IL-ls. The present results demonstrate that microglia and astrocytes are sources of brain IL- ls and add a new member to the family of cytokines produced in the brain. ( C) 1999 Elsevier Science B.V. All rights reserved.