Elevated expression of IFN-gamma in the HIV-1 infected brain

Paul Shapshak, Robert Duncan, Alireza Minagar, Pura Rodriguez De La Vega, Renée V. Stewart, Karl Goodkin

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1073-1081
Number of pages9
JournalFrontiers in Bioscience
Volume9
StatePublished - Aug 24 2004
Externally publishedYes

Fingerprint

Viruses
HIV-1
Brain
Interleukin-4
Tumor Necrosis Factor-alpha
Cytokines
Dementia
Opportunistic Infections
Virus Diseases
Tissue
T-cells
Macrophages
Alkaline Phosphatase
Toxicity
Brain Diseases
Temporal Lobe

Keywords

  • Cytokines
  • HIV associated dementia
  • HIV-1
  • IFN-gamma
  • IL-4
  • Immunohistochemistry
  • NeuroAIDS
  • Neuropsychiatric impairment
  • TNF-alpha

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Shapshak, P., Duncan, R., Minagar, A., Rodriguez De La Vega, P., Stewart, R. V., & Goodkin, K. (2004). Elevated expression of IFN-gamma in the HIV-1 infected brain. Frontiers in Bioscience, 9, 1073-1081.

Elevated expression of IFN-gamma in the HIV-1 infected brain. / Shapshak, Paul; Duncan, Robert; Minagar, Alireza; Rodriguez De La Vega, Pura; Stewart, Renée V.; Goodkin, Karl.

In: Frontiers in Bioscience, Vol. 9, 24.08.2004, p. 1073-1081.

Research output: Contribution to journalArticle

Shapshak, P, Duncan, R, Minagar, A, Rodriguez De La Vega, P, Stewart, RV & Goodkin, K 2004, 'Elevated expression of IFN-gamma in the HIV-1 infected brain', Frontiers in Bioscience, vol. 9, pp. 1073-1081.
Shapshak P, Duncan R, Minagar A, Rodriguez De La Vega P, Stewart RV, Goodkin K. Elevated expression of IFN-gamma in the HIV-1 infected brain. Frontiers in Bioscience. 2004 Aug 24;9:1073-1081.
Shapshak, Paul ; Duncan, Robert ; Minagar, Alireza ; Rodriguez De La Vega, Pura ; Stewart, Renée V. ; Goodkin, Karl. / Elevated expression of IFN-gamma in the HIV-1 infected brain. In: Frontiers in Bioscience. 2004 ; Vol. 9. pp. 1073-1081.
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