{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T11:00:06Z","timestamp":1770721206456,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":3509,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1995,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Microglial cell activation, myelin alteration, and abundant tumor necrosis factor (TNF)\u2010\u03b1 message have been observed in the brains of some human immunodeficiency virus type 1 (HIV \u2010 1)vinfected and demented patients. We therefore used cultures of purified human microglia and oligodendrocytes derived from adult human brain to examine the role of TNF\u2010\u03b1 in HIV\u20101 encephalopathy. Human microglia synthesize TNF\u2010\u03b1 message and protein in vitro. When these cells were infected with HIV\u20101 JrFL and maintained in the presence of TNF\u2010\u03b1 antibodies, soluble TNF\u2010\u03b1 receptors, or the TNF\u2010\u03b1 inhibitor pentoxifylline, viral replication was delayed or strongly inhibited. Both human microglia and oligodendrocytes express the two TNF receptors, TNF\u2010Rl, which has been implicated in cytotoxicity, and TNF\u2010R2. While TNF\u2010\u03b1 may enhance HIV\u20101 replication in an autocrine manner, it is not toxic for microglia. In contrast, recombinant human TNF\u2010\u03b1 causes oligodendrocyte death in a dose\u2010dependent manner. In situ detection of DNA fragmentation in some cells indicated that oligodendrocyte death may occur by apoptosis. Addition of live microglia or medium conditioned by these cells also resulted in 30 to 40% oligodendrocyte death, which was largely prevented by TNF\u2010\u03b1 inhibitors. We propose that TNF\u2010\u03b1 plays a dual role in HIV\u20101 encephalopathy, enhancing viral replication by activated microglia and damaging oligodendrocytes. Thus, TNF\u2010\u03b1 inhibitors may alleviate some ofthe neurological manifestations of acquired immunodeficiency syndrome.<\/jats:p>","DOI":"10.1002\/ana.410370315","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T16:14:15Z","timestamp":1104596055000},"page":"381-394","source":"Crossref","is-referenced-by-count":102,"title":["In vitro evidence for a dual role of tumor necrosis factor\u2010\u03b1 in human immunodeficiency virus type 1 encephalopathy"],"prefix":"10.1002","volume":"37","author":[{"given":"Susan G.","family":"Wilt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Milward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia 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