Dexamethasone therapy worsens the neuropathology of human immunodeficiency virus type 1 encephalitis in SCID mice

Jenae Limoges, Yuri Persidsky, Paul Bock, Howard E. Gendelman

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Human immunodeficiency virus (HIV) dementia is a late complication of viral infection. Cognitive dysfunction revolves around the secretion of neurotoxins from immunologically competent virus-infected brain macrophages and microglia. Such macrophage neurotoxins are inflammatory factors that produce selective neuronal dysfunction and ultimately cell death. To evaluate the potential efficacy of antiinflammatory therapy for HIV dementia, dexamethasone was administered to severe combined immunodeficient mice with HIV-1 encephalitis. Mice were given therapeutic doses of dexamethasone before intracerebral inoculation with HIV-1-infected human monocytes. Histochemical evaluation showed a worsening of neuropathology after treatment, with astrogliosis and increased apoptosis of neurons. Laboratory investigation of the mechanisms for the dexamethasone effects revealed increased viability of HIV-infected macrophages and incomplete suppression of neurotoxic inflammatory secretions. The results suggest the need for caution in administering glucocorticoids for treatment of HIV encephalitis in humans.

Original languageEnglish (US)
Pages (from-to)1368-1381
Number of pages14
JournalJournal of Infectious Diseases
Volume175
Issue number6
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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