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

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

Mol Med. 1996 Jan;2(1):27-37. Unique Identifier : AIDSLINE MED/97056192
Lane TE; Buchmeier MJ; Watry DD; Fox HS; Department of Neuropharmacology, Scripps Research Institute, La; Jolla, California 92037, USA.

Abstract: BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to severe impairments in cognition, behavior, and motor skills. The mechanism(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-gamma (IFNgamma), and interleukin 1 beta (IL-1 beta) 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, IFN gamma, and IL-1 beta 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.

Keywords: Amino Acid Sequence Animal Base Sequence Brain/ENZYMOLOGY/VIROLOGY Central Nervous System/METABOLISM/VIROLOGY Cloning, Molecular Gene Expression Regulation/GENETICS Human HIV/METABOLISM In Situ Hybridization/METHODS Interferon Type II/ANALYSIS Interleukin-1/ANALYSIS Lipopolysaccharides/PHARMACOLOGY Microglia/METABOLISM Molecular Sequence Data Nitrates/CEREBROSPINAL FLUID/METABOLISM Nitric-Oxide Synthase/*METABOLISM Nitrites/CEREBROSPINAL FLUID/METABOLISM Polymerase Chain Reaction RNA, Messenger/ANALYSIS/GENETICS Sequence Alignment Sequence Analysis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. SIV/*METABOLISM JOURNAL ARTICLE
970228
M9721921

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