title: Morphine potentiates neuropathogenesis of SIV infection in rhesus macaques.
abstract: 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.
authors: Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors: Sirosh M
authors: SM
authors: Bokhari
authors: Ramakrishna
authors: R
authors: Hegde
authors: Shannon
authors: S
authors: Callen
authors: Honghong
authors: H
authors: Yao
authors: Istvan
authors: I
authors: Adany
authors: Qingsheng
authors: Q
authors: Li
authors: Zhuang
authors: Z
authors: Li
authors: David
authors: D
authors: Pinson
authors: Hung-Wen
authors: HW
authors: Yeh
authors: Paul D
authors: PD
authors: Cheney
authors: Shilpa
authors: S
authors: Buch
mesh_terms: D000818:Animals; D018450:Disease Progression; D005434:Flow Cytometry; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008253:Macaca mulatta; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology* / Q000821:virology*; D019562:Viral Load / Q000187:drug effects
chemical_list: D009294:Narcotics; D009020:Morphine