IMR Press / FBL / Volume 9 / Issue 2 / DOI: 10.2741/1271

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Elevated expression of IFN-gamma in the HIV-1 infected brain
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1 Departments of Psychiatry and Behavioral Sciences, University of Miami Medical School, Miami, Florida
2 Departments of Neurology, University of Miami Medical School, Miami, Florida
3 Departments of Pathology, University of Miami Medical School, Miami, Florida
4 Departments of Epidemiology, University of Miami Medical School, Miami, Florida
5 Departments of Comprehensive Drug Research Center, University of Miami Medical School, Miami, Florida
6 Departments of Neurology, Psychiatry and Anesthesiology, Louisiana State University School of Medicine, Shreveport, Louisiana
7 Florida International University, Miami, Florida
8 Miami-Dade Community College, Miami, Florida
Front. Biosci. (Landmark Ed) 2004, 9(2), 1073–1081; https://doi.org/10.2741/1271
Published: 1 May 2004
Abstract

We determined the extent of expression of three cytokines (IFN-gamma, IL-4, and TNF-alpha ) in brain tissue infected with human immunodeficiency virus-1 (HIV-1). The selections were IFN-gamma as a Th1 cytokine, IL- 4 as a Th2 cytokine, and TNF-alpha as a pro-inflammatory cytokine (and because of its prior implication in brain tissue damage due to HIV-1 infection). Based on current models for pathogenesis of HIV-1-associated dementia (HAD), in the periphery, Th1 cytokines are considered to be salutary, whereas Th2 cytokines are regarded as deleterious. However, we hypothesized that in the CNS these roles are reversed. Post-mortem temporal lobe tissue specimens from 16 HIV-1-seropositive patients and 11 HIV-1-seronegative controls were stained for IFN-gamma, IL-4, and TNF-alpha utilizing immunohistochemistry and alkaline phosphatase. HIV-1 infection causes alterations of brain cytokine expression that include increased IFN-gamma expression for HIV-1-seropositive vs. HIV-1-seronegative individuals. There was increased expression of IFN-gamma for HIV-1-seropositive individuals with or without HAD, with or without the broader category of neuropsychiatric impairment (NPI), and with or without opportunistic infections (OIs) compared to HIV-1-seronegatives. A significant inverse correlation between IFN-gamma vs. IL-4 in HIV-1-seropositives with HAD and in seronegative individuals was observed. There was an inverse correlation in seropositives between IFN-gamma vs. TNF-alpha, a positive trend with HAD, significant without HAD, significant with NPI and significant without OIs. Between IL-4 vs. TNF-alpha there was a correlation (trend) in seropositives, a trend with NPI, significant without NPI, and a trend without OI. Due to HIV-1 infection of the brain and neurological disease there is a prominent increased expression of IFN-gamma, an inverse expression of IFN-gamma vs. TNF-alpha, and TNF-alpha vs. IL-4. The inverse correlation between increased IFN-gamma and decreased IL-4 expression is consistent with the stimulation of activated macrophages, and T cells, greater toxicity in the HIV-1-infected brain, and is supportive of the significance of IFN-gamma in HIV-1-infected patients.

Keywords
HIV-1
Cytokines
IFN-gamma
IL-4
TNFalpha
Immunohistochemistry
NeuroAIDS
HIV associated dementia
Neuropsychiatric impairment
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