Neuroprotective and Anti–Human Immunodeficiency Virus Activity of Minocycline
| Autor: | Janice E. Clements, Patrick M. Tarwater, Brandon T. Bullock, Sheila A. Barber, Jennifer L. Uhrlaub, Joseph L. Mankowski, M. Christine Zink, Jesse B. DeWitt, Tauni Voelker |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Central Nervous System
AIDS Dementia Complex Anti-Inflammatory Agents Simian Acquired Immunodeficiency Syndrome Minocycline Inflammation Virus Replication medicine.disease_cause p38 Mitogen-Activated Protein Kinases Neuroprotection Virus medicine Animals Encephalitis Viral Lymphocytes Cells Cultured Chemokine CCL2 biology business.industry Macrophages HIV General Medicine Viral Load Simian immunodeficiency virus medicine.disease biology.organism_classification Virology Anti-Bacterial Agents Disease Models Animal Neuroprotective Agents Lentivirus Immunology Simian Immunodeficiency Virus Macaca nemestrina medicine.symptom business Viral load Biomarkers Encephalitis medicine.drug |
| Zdroj: | JAMA. 293:2003 |
| ISSN: | 0098-7484 |
| Popis: | ContextThe prevalence of human immunodeficiency virus (HIV) central nervous system (CNS) disease has not decreased despite highly active antiretroviral therapy. Current antiretroviral drugs are expensive, have significant adverse effects including neurotoxicity, and few cross the blood-brain barrier.ObjectiveTo examine the ability of minocycline, an antibiotic with potent anti-inflammatory and neuroprotective properties, to protect against encephalitis and neurodegeneration using a rapid, high viral load simian immunodeficiency virus (SIV) model of HIV-associated CNS disease that constitutes a rigorous in vivo test for potential therapeutics.Design and SubjectsFive SIV-infected pigtailed macaques were treated with 4 mg/kg per day of minocycline beginning at early asymptomatic infection (21 days after inoculation). Another 6 macaques were inoculated with SIV but remained untreated. Blood and cerebrospinal fluid (CSF) samples were taken on days 7, 10, 14, 21, 28, 35, 43, 56, 70, 77, and 84, and all macaques were humanely killed at 84 days after inoculation, a time that corresponds to late-stage infection in HIV-infected individuals.Main Outcome MeasuresBlood and CSF samples were tested for viral load by real-time reverse transcription–polymerase chain reaction and levels of monocyte chemoattractant protein 1 were quantitated by enzyme-linked immunosorbent assay. The presence and severity of encephalitis was determined by microscopic examination of tissues. Central nervous system inflammation was further assessed by measuring infiltration and activation of macrophages, activation of p38 mitogen-activated protein kinase and expression of amyloid precursor protein by quantitative immunohistochemistry.ResultsMinocycline-treated macaques had less severe encephalitis (P = .02), reduced CNS expression of neuroinflammatory markers (major histocompatibility complex class II, P = .03; macrophage marker CD68 , P = .07; T-cell intracytoplasmic antigen 1, P = .03; CSF monocyte chemoattractant protein 1, P = .001), reduced activation of p38 mitogen-activated protein kinase (P |
| Databáze: | OpenAIRE |
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