Morphine Potentiates Neuropathogenesis of SIV Infection in Rhesus Macaques

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• 作者：Sirosh M. Bokhari (4)
  Ramakrishna Hegde (1)
  Shannon Callen (6)
  Honghong Yao (6)
  Istvan Adany (1)
  Qingsheng Li (5)
  Zhuang Li (1)
  David Pinson (3)
  Hung-Wen Yeh (2)
  Paul D. Cheney (1)
  Shilpa Buch (1) (6)
  
• 关键词：Morphine ; SIV ; Neuropathogenesis
• 刊名：Journal of Neuroimmune Pharmacology
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：6
• 期：4
• 页码：626-639
• 全文大小：902KB
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• 作者单位：Sirosh M. Bokhari (4)
  Ramakrishna Hegde (1)
  Shannon Callen (6)
  Honghong Yao (6)
  Istvan Adany (1)
  Qingsheng Li (5)
  Zhuang Li (1)
  David Pinson (3)
  Hung-Wen Yeh (2)
  Paul D. Cheney (1)
  Shilpa Buch (1) (6)
  
  4. Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, St Louis, MO, 63110, USA
  1. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
  6. Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center (DRC 8011), University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA
  5. Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA
  3. Department of Pathology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
  2. Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, 66160, USA
  
• ISSN：1557-1904

文摘

Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Opiates are well known to modulate immune responses by preventing the development of cell-mediated immune responses. Their effect on the pathogenesis of HIV-1 infection however remains controversial. Using the simian immunodeficiency virus/macaque model of HIV pathogenesis, we sought to explore the impact of morphine on disease progression and pathogenesis. Sixteen rhesus macaques were divided into two groups; four were administered saline and 12 others morphine routinely. Both groups of animals were then inoculated with SIVmacR71/17E and followed longitudinally for disease pathogenesis. The morphine group (M+V) exhibited a trend towards higher mortality rates and retardation in weight gain compared to the virus-alone group. Interestingly, a subset of M+V animals succumbed to disease within weeks post-infection. These rapid progressors also exhibited a higher incidence of other end-organ pathologies. Despite the higher numbers of circulating CD4+ and CD8+ T cells in the M+V group, CD4/CD8 ratios between the groups remained unchanged. Plasma and CSF viral load in the M+V group was at least a log higher than the control group. Similarly, there was a trend toward increased virus build-up in the brains of M+V animals compared with controls. A novel finding of this study was the increased influx of infected monocyte/macrophages in the brains of M+V animals.