Interaction between HIV and intravenous heroin abuse?

Everall, Ian

doi:10.1016/j.jneuroim.2003.10.008

Cited by 15 publications

(12 citation statements)

References 32 publications

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“…Effects include increases in tumor necrosis factor-α (TNF-α) production (Chao et al, 1994) and upregulation of CCR5 and CXCR4 [see (Rogers and Peterson, 2003)], heterologous cross-sensitization of CCR5 (McCarthy et al, 2001;Rogers and Peterson, 2003), and alterations in HIV propagation in lymphocytes and monocytes/macrophages [reviewed in (McCarthy et al, 2001;Rogers and Peterson, 2003)]. Although the prevalence of HIV infection among opiate abusers is substantial, and opiates may accelerate the frequency and severity of HIV encephalitis (HIVE) (Bell et al, 1998;Nath et al, 2000;Nath et al, 2002), other evidence suggest that opiates can allay systemic HIV infection (Donahoe and Vlahov, 1998;Everall, 2004;Donahoe, 2004). The deleterious effects may be particularly evident in the CNS (Donahoe, 2004) and whether opiates are good, bad or act indifferently likely varies among cell types and depends on the parameter measured (Khurdayan et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Synergistic increases in intracellular Ca²⁺, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat

El‐Hage

Gurwell

Singh

et al. 2005

Glia

207

257

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Recent evidence suggests that injection drug users who abuse heroin are at increased risk for CNS complications from human immunodeficiency virus (HIV) infection. Opiate drugs may intrinsically alter the pathogenesis of HIV by directly modulating immune function and by directly modifying the CNS response to HIV. Despite this, the mechanisms by which opiates increase the neuropathogenesis of HIV are uncertain. Herein we describe the effect of morphine and the HIV-1 protein toxin Tat 1-72 on astroglial function in cultures derived from ICR mice. Astroglia maintain the blood brain barrier and influence inflammatory signaling in the CNS. Astrocytes can express μ opioid receptors, and are likely targets for abused opiates, which preferentially activate μ-opioid receptors. While Tat alone disrupts astrocyte function, when combined with morphine, Tat causes synergistic increases in [Ca 2+ ] i. . Moreover, astrocyte cultures treated with morphine and Tat showed exaggerated increases in chemokine release including monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES), as well as interleukin-6 (IL-6). Morphine-Tat interactions were prevented by the μ-opioid receptor antagonist β-funaltrexamine, or by immunoneutralizing Tat 1-72 or substituting a non-toxic, deletion mutant (Tat Δ31-61 ). Our findings suggest that opiates may increase the vulnerability of the CNS to viral entry (via recruitment of monocytes/macrophages) and ensuing HIV encephalitis by synergistically increasing MCP-1 and RANTES release by astrocytes. The results further suggest ‡ Abbreviations: alpha chemokine receptor (CXCR); beta chemokine ligand (CCL); beta chemokine receptor (CCR); β-funaltrexamine (β-FNA); calcium-induced calcium release (CICR); excitatory amino acid transporter-2 (EAAT2); granulocyte macrophage colony stimulating factor (GM-CSF); granulocyte-colony stimulating factor (G-CSF); human immunodeficiency virus (HIV); human immunodeficiency virus encephalitis (HIVE); inositol trisphosphate (IP 3 ); interferon (IFN); interleukin (IL); intracellular Ca 2+ ([Ca 2+ ] i ); monocyte chemoattractant protein (MCP); nor-binaltorphimine (nor-BNI); phosphatidylinositol 3-kinase (PI3-kinase); phospholipase C-γ (PLCγ); regulated on activation, normal T cell expressed and secreted (RANTES); soluble TNF receptor subunit (sTNFR1); stem cell factor (SCF); thrombopoietin (TPO); transactivator of transcription (Tat); tumor necrosis factor-α (TNF-α); vascular endothelial growth factor (VEGF).

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Section: Introductionmentioning

confidence: 99%

Synergistic increases in intracellular Ca²⁺, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat

El‐Hage

Gurwell

Singh

et al. 2005

Glia

207

257

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“…The results of various epidemiological studies vary with some showing that opiates may have a protective role (Spijkerman et al, 1995; Spijkerman et al, 1996a), others showing a deleterious role (Bouwman et al, 1998; Hutchinson et al, 1997; Krol et al, 1999), and still others finding no effect (Pezzotti et al, 1999; Prins and Veugelers, 1997; Thorpe et al, 2004) on HIV-related pathology and/or mortality rates. Unfortunately, human studies are often confounded by differences in drug abuse pattern and duration, polydrug use, as well as widespread implementation of antiviral therapies (Everall, 2004; Kapadia et al, 2005). However, a recent study by Thorpe et al (2004), based on a large population of HIV-infected women who were either “hard-drug” users or not, is significant in that it was possible to achieve better control of multiple variables.…”

Section: Introductionmentioning

confidence: 99%

Rhesus Macaque Model of Chronic Opiate Dependence and Neuro-AIDS: Longitudinal Assessment of Auditory Brainstem Responses and Visual Evoked Potentials

Riazi

Marcario

Samson

et al. 2009

J Neuroimmune Pharmacol

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Our work characterizes the effects of opiate (morphine) dependence on auditory brainstem and visual evoked responses in a rhesus macaque model of neuro-AIDS utilizing a chronic continuous drug delivery paradigm. The goal of this study was to clarify whether morphine is protective, or if it exacerbates simian immunodeficiency virus (SIV) related systemic and neurological disease. Our model employs a macrophage tropic CD4/CCR5 co-receptor virus, SIVmac239 (R71/E17), which crosses the blood brain barrier shortly after inoculation and closely mimics the natural disease course of human immunodeficiency virus (HIV) infection. The cohort was divided into 3 groups: morphine only, SIV only, and SIV + morphine. Evoked potential (EP) abnormalities in sub-clinically infected macaques were evident as early as eight weeks post-inoculation. Prolongations in EP latencies were observed in SIV-infected macaques across all modalities. Animals with the highest CSF viral loads and clinical disease showed more abnormalities than those with sub-clinical disease, confirming our previous work (Raymond et al, 1998, 1999, 2000). Although some differences were observed in auditory and visual evoked potentials in morphine treated compared to untreated SIV-infected animals, the effects were relatively small and not consistent across evoked potential type. However, morphine treated animals with subclinical disease had a clear tendency toward higher virus loads in peripheral and CNS tissues (Marcario et al., 2008) suggesting that if had been possible to follow all animals to end-stage disease, a clearer pattern of evoked potential abnormality might have emerged.

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“…In addition to experimental findings, epidemiological studies are beginning to establish links between opiate drug use and acquired immunodeficiency syndrome (AIDS) progression Donahoe and Vlahov, 1998), although the extent to which opiates per se contribute to AIDS progression remains controversial (Ansari, 2004;Donahoe, 2004;Everall, 2004). It is important to consider, however, that the effects of opiates on systemic immune function and HIV progression may not be readily extrapolated to their effects in the CNS, which appear to be preferentially vulnerable to opiate drug-HIV interactions Nath et al, 2002;Donahoe, 2004;El-Hage et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

HIV‐1 Tat and opiate‐induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP‐1 and alternative chemokines

El‐Hage

Wang

et al. 2005

Glia

143

150

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Opiates exacerbate human immunodeficiency virus type 1 (HIV-1) Tat(1-72)-induced release of key proinflammatory cytokines by astrocytes, which may accelerate HIV neuropathogenesis in opiate abusers. The release of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), in particular, is potentiated by opiate-HIV Tat interactions in vitro. Although MCP-1 draws monocytes/macrophages to sites of CNS infection, and activated monocytes/microglia release factors that can damage bystander neurons, the role of MCP-1 in neuro-acquired immunodeficiency syndrome (neuroAIDS) progression in opiate abusers, or nonabusers, is uncertain. Using a chemotaxis assay, N9 microglial cell migration was found to be significantly greater in conditioned medium from mouse striatal astrocytes exposed to morphine and/or Tat(1-72) than in vehicle-, mu-opioid receptor (MOR) antagonist-, or inactive, mutant Tat(delta31-61)-treated controls. Conditioned medium from astrocytes treated with morphine and Tat caused the greatest increase in motility. The response was attenuated using conditioned medium immunoneutralized with MCP-1 antibodies, or medium from MCP-1(-/-) astrocytes. In the presence of morphine (time-release, subcutaneous implant), intrastriatal Tat increased the proportion of neural cells that were astroglia and F4/80+ macrophages at 7 days post-injection. This was not seen after treatment with Tat alone, or with morphine plus inactive Tat(delta31-61) or naltrexone. Glia displayed increased MOR and MCP-1 immunoreactivity after morphine and/or Tat exposure. The findings indicate that MCP-1 underlies most of the response of microglia, suggesting that one way in which opiates exacerbate neuroAIDS is by increasing astroglial-derived proinflammatory chemokines at focal sites of CNS infection and promoting macrophage entry and local microglial activation. Importantly, increased glial expression of MOR can trigger an opiate-driven amplification/positive feedback of MCP-1 production and inflammation.

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Interaction between HIV and intravenous heroin abuse?

Cited by 15 publications

References 32 publications

Synergistic increases in intracellular Ca²⁺, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat

Synergistic increases in intracellular Ca²⁺, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat

Rhesus Macaque Model of Chronic Opiate Dependence and Neuro-AIDS: Longitudinal Assessment of Auditory Brainstem Responses and Visual Evoked Potentials

HIV‐1 Tat and opiate‐induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP‐1 and alternative chemokines

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Interaction between HIV and intravenous heroin abuse?

Cited by 15 publications

References 32 publications

Synergistic increases in intracellular Ca2+, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat

Synergistic increases in intracellular Ca2+, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat

Rhesus Macaque Model of Chronic Opiate Dependence and Neuro-AIDS: Longitudinal Assessment of Auditory Brainstem Responses and Visual Evoked Potentials

HIV‐1 Tat and opiate‐induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP‐1 and alternative chemokines

Contact Info

Product

Resources

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Synergistic increases in intracellular Ca²⁺, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat

Synergistic increases in intracellular Ca²⁺, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat