{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T05:52:33Z","timestamp":1774677153226,"version":"3.50.1"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,12,1]]},"abstract":"<jats:p>Human immunodeficiency virus (HIV) infection of brain macrophages and astroglial proliferation are central features of HIV-induced central nervous system (CNS) disorders. These observations suggest that glial cellular interactions participate in disease. In an experimental system to examine this process, we found that cocultures of HIV-infected monocytes and astroglia release high levels of cytokines and arachidonate metabolites leading to neuronotoxicity. HIV-1ADA-infected monocytes cocultured with human glia (astrocytoma, neuroglia, and primary human astrocytes) synthesized tumor necrosis factor (TNF-alpha) and interleukin 1 beta (IL-1 beta) as assayed by coupled reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and biological activity. The cytokine induction was selective, cell specific, and associated with induction of arachidonic acid metabolites. TNF-beta, IL-1 alpha, IL-6, interferon alpha (IFN-alpha), and IFN-gamma were not produced. Leukotriene B4, leukotriene D4, lipoxin A4, and platelet-activating factor were detected in large amounts after high-performance liquid chromatography separation and correlated with cytokine activity. Specific inhibitors of the arachidonic cascade markedly diminished the cytokine response suggesting regulatory relationships between these factors. Cocultures of HIV-infected monocytes and neuroblastoma or endothelial cells, or HIV-infected monocyte fluids, sucrose gradient-concentrated viral particles, and paraformaldehyde-fixed or freeze-thawed HIV-infected monocytes placed onto astroglia failed to induce cytokines and neuronotoxins. This demonstrated that viable monocyte-astroglia interactions were required for the cell reactions. The addition of actinomycin D or cycloheximide to the HIV-infected monocytes before coculture reduced, &amp;gt; 2.5-fold, the levels of TNF-alpha. These results, taken together, suggest that the neuronotoxicity associated with HIV central nervous system disorders is mediated, in part, through cytokines and arachidonic acid metabolites, produced during cell-to-cell interactions between HIV-infected brain macrophages and astrocytes.<\/jats:p>","DOI":"10.1084\/jem.176.6.1703","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1703-1718","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":387,"title":["Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease."],"prefix":"10.1084","volume":"176","author":[{"given":"P","family":"Genis","sequence":"first","affiliation":[{"name":"Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Jett","sequence":"additional","affiliation":[{"name":"Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E W","family":"Bernton","sequence":"additional","affiliation":[{"name":"Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Boyle","sequence":"additional","affiliation":[{"name":"Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H A","family":"Gelbard","sequence":"additional","affiliation":[{"name":"Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Dzenko","sequence":"additional","affiliation":[{"name":"Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R W","family":"Keane","sequence":"additional","affiliation":[{"name":"Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Resnick","sequence":"additional","affiliation":[{"name":"Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Mizrachi","sequence":"additional","affiliation":[{"name":"Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D J","family":"Volsky","sequence":"additional","affiliation":[{"name":"Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1992,12,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/176\/6\/1703\/1673838\/1703.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/176\/6\/1703\/1673838\/1703.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T04:48:41Z","timestamp":1690260521000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/176\/6\/1703\/24752\/Cytokines-and-arachidonic-metabolites-produced"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,12,1]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1992,12,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.176.6.1703","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,12,1]]}}}