Expression of inflammatory cytokines and inducible nitric oxide synthase in brains of SIV-Infected rhesus monkeys: Applications to HIV-induced central nervous system disease

Thomas E. Lane, Michael J. Buchmeier, Debbie D. Watry, Howard S. Fox

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Abstract

Background: Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to severe impairnents in cognition, behavior, and motor skills. The mechanisms(s) by which HIV-1 induces CNS disease are not well understood. Recent evidence suggests that expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) may contribute to HIV-1-induced neurologic disease. We sought to determine if these factors were present in the CNS of rhesus monkeys with simian immunodeficiency virus (SIV)-induced CNS disease. Materials and Methods: Total NO production in cerebral spinal fluid (CSF) from infected monkeys was determined by measuring nitrite (NO2-) and nitrate (NO3-) (stable NO degradation products) utilizing Greiss reagents. In situ hybridization revealed iNOS, interferon- γ (IFNγ), and interleukin 1β (IL-1β) mRNA in the brains of SIV-infected monkeys. Microglia were isolated from animals infected with SIV. Following stimulation with LPS, induction of iNOS mRNA in isolated microglia was analyzed by reverse transcriptase-polymerase chain reaction. Results: Serial CSF samples from an SIV-infected monkey reveal increased levels of NO2- /NO3-. In situ hybridization demonstrated iNOS, IFNγ, and IL-1β mRNAs in post-mortem brain tissue of SIV-infected monkeys. Furthermore, stimulated microglia from an SIV-infected monkey could produce iNOS mRNA. Conclusions: The presence of iNOS in the brain and NO2-/NO3- in the CSF indicates that NO is produced in the CNS of SIV-infected monkeys. The data suggest that iNOS and NO may be contributing to SIV-induced CNS disease.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalMolecular Medicine
Volume2
Issue number1
StatePublished - Dec 30 1996

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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