Dexamethasone therapy worsens the neuropathology of human immunodeficiency virus type 1 encephalitis in SCID mice.
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.
Limoges
J
J
Department of Pathology, and the Eppley Institute for Research in Cancer and Allied Medicine, University of Nebraska Medical Center, Omaha 68198-5215, USA.
Persidsky
Y
Y
Bock
P
P
Gendelman
H E
HE
D015526:AIDS Dementia Complex / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000473:pathology* / Q000821:virology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation; D003907:Dexamethasone / Q000009:adverse effects* / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis; D004195:Disease Models, Animal; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D017628:Microglia / Q000473:pathology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology; D009474:Neurons / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D003907:Dexamethasone; D015232:Dinoprostone