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M9460553.TXT
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1994-06-25
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Document 0553
DOCN M9460553
TI Elevated central nervous system prostaglandins in human immunodeficiency
virus-associated dementia.
DT 9408
AU Griffin DE; Wesselingh SL; McArthur JC; Department of Neurology, Johns
Hopkins University School of; Medicine, Baltimore, MD.
SO Ann Neurol. 1994 May;35(5):592-7. Unique Identifier : AIDSLINE
MED/94234691
AB The dementia associated with human immunodeficiency virus (HIV) is
poorly understood. Dementia is accompanied by infection and activation
of macrophage lineage cells in the brain and production of toxic
products by these cells has been postulated to play a role in the
pathogenesis of dementia. Eicosanoids are potential products of
activated macrophages that can mediate cell injury. We measured the
levels of prostaglandin E2 in the cerebrospinal fluid of HIV-positive
individuals with dementia and/or myelopathy and compared these levels
with those of HIV-negative patients with other neurological diseases and
HIV-positive patients without dementia. Cerebrospinal fluid
prostaglandin E2 levels were increased in dementia. This increase was
associated with severity of dementia and correlated with cerebrospinal
fluid levels of neopterin and beta 2-microglobulin. Prostaglandins F2
alpha and thromboxane B2, additional products of the cyclooxygenase
pathway of arachidonic acid metabolism, were also elevated in dementia,
but leukotriene C4, a product of the lipoxygenase pathway was not. Since
synthesis of prostaglandins is regulated in part by the levels of
inducible forms of cyclooxygenase, we measured the levels of
cyclooxygenase-1 and 2 mRNAs in the brains of HIV-positive individuals
with and without dementia by reverse transcriptase polymerase chain
reaction. Levels of intact cyclooxygenase-1 mRNA were higher in the
brains of demented individuals, but this did not reach statistical
significance. These data demonstrate that prostaglandins are increased
in the central nervous system in HIV-associated dementia and may play a
role in the development of neurological dysfunction.
DE AIDS Dementia Complex/*CEREBROSPINAL FLUID Base Sequence
Brain/METABOLISM Cohort Studies Dinoprostone/*CEREBROSPINAL FLUID
Human HIV Seropositivity/CEREBROSPINAL FLUID Leukocyte Count
Longitudinal Studies Molecular Sequence Data Polymerase Chain Reaction
Prostaglandin-Endoperoxide Synthase/METABOLISM Radioimmunoassay
Reference Values RNA, Messenger/ANALYSIS Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S. T4 Lymphocytes JOURNAL ARTICLE
MULTICENTER STUDY
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).