Glial cytokines as neuropathogenic factors in HIV infection: pathogenic similarities to Alzheimer's disease.
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.
Stanley
L C
LC
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
Mrak
R E
RE
Woody
R C
RC
Perrot
L J
LJ
Zhang
S
S
Marshak
D R
DR
Nelson
S J
SJ
Griffin
W S
WS
D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology; D006679:HIV Seropositivity / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009418:S100 Proteins / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D007375:Interleukin-1; D009418:S100 Proteins; D016875:tau Proteins