Document 0278
 DOCN  M9460278
 TI    Glial cytokines as neuropathogenic factors in HIV infection: pathogenic
       similarities to Alzheimer's disease.
 DT    9408
 AU    Stanley LC; Mrak RE; Woody RC; Perrot LJ; Zhang S; Marshak DR; Nelson
       SJ; Griffin WS; Department of Pediatrics, University of Arkansas for
       Medical; Sciences, Little Rock.
 SO    J Neuropathol Exp Neurol. 1994 May;53(3):231-8. Unique Identifier :
       AIDSLINE MED/94231204
 AB    The mechanisms by which human immunodeficiency virus (HIV) infection
       provokes progressive neurodegeneration and dementia in acquired
       immunodeficiency syndrome (AIDS) remain obscure. In HIV-infected (HIV+)
       individuals, we found that the brain cells preferentially infected by
       HIV, viz. the microglia, were abundant, activated, and intensely
       immunopositive for interleukin-1 alpha (IL-1 alpha), an immune
       response-generated cytokine that increases the synthesis and processing
       of beta-amyloid precursor proteins (beta-APP) and promotes proliferation
       and activation of astroglia. We also found an increase in the number of
       activated astroglia expressing elevated levels of S100 beta, a cytokine
       that increases intraneuronal calcium levels and promotes excessive
       growth of neuronal processes (neurites). These glial changes were
       accompanied by increased expression of beta-APP immunoreaction product
       in neurons and overgrown (dystrophic) neurites. In addition, some
       neurons contained monoclonal antibody Tau-2 immunopositive,
       neurofibrillary tangle-like structures. Our findings provide evidence
       that glial activation with increased expression of IL-1 alpha and S100
       beta may be important in the neuropathogenesis of AIDS dementia. We
       propose that HIV infection promotes excessive microglial IL-1 alpha
       expression with consequent astrogliosis and increased expression of S100
       beta. Overexpression of these two cytokines may then be involved in AIDS
       neuropathogenesis by inducing gliosis, growth of dystrophic neurites,
       and calcium-mediated neuronal cell loss in AIDS.
 DE    tau Proteins/METABOLISM  Adult  Alzheimer's
       Disease/*METABOLISM/PATHOLOGY  Amyloid beta-Protein Precursor/METABOLISM
       Brain/*METABOLISM/PATHOLOGY  Female  Human  HIV
       Infections/*METABOLISM/PATHOLOGY  HIV
       Seropositivity/METABOLISM/PATHOLOGY  Interleukin-1/*METABOLISM  Male
       Microglia/*METABOLISM/PATHOLOGY  Nerve Tissue Protein S 100/METABOLISM
       Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).