HIV-1, HCV and Alcohol in the CNS: Potential Interactions and Effects on Neuroinflammation

Silverstein, Peter S.; Kumar, Santosh; Kumar, Anil

doi:10.2174/1570162x12666140721122956

Cited by 20 publications

(13 citation statements)

References 103 publications

(126 reference statements)

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“…Further, acute or chronic alcohol consumption has been reported to increase HIV replication [ 59 , 60 ] and dysregulate cytokine production [ 61 , 62 ], it is also associated with poor adherence to ART therapy [ 63 , 64 ]. Alcohol abuse also causes neuro-inflammation [ 65 , 66 ] and increases the risk of secondary infections [ 67 ], thereby decreasing survival rates in HIV patients [ 68 ]. In our study, we investigated cytokine levels in exosomes of HIV-positive alcohol drinkers to find a potential marker to diagnose alcohol-induced toxicity in HIV patients.…”

Section: Discussionmentioning

confidence: 99%

Cytokine profiling of exosomes derived from the plasma of HIV-infected alcohol drinkers and cigarette smokers

et al. 2018

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Cytokines and chemokines circulate in plasma and may be transferred to distant sites, via exosomes. HIV infection is associated with dysregulation of cytokines and chemokines, which subsequently contribute to the pathogenesis of HIV. Alcohol and tobacco exposure, which are prevalent in HIV-infected individuals, may induce changes in the expression of cytokines and chemokines. Therefore, our aim in this study was to quantify plasma exosomal cytokines and chemokines that we expect to exacerbate toxicity or disease progression in HIV-positive drug abusers. We measured the levels of cytokines and chemokines in the plasma and plasma exosomes of 39 patients comprising six groups: HIV-negative and HIV-positive non drug abusers, HIV-negative and HIV-positive alcohol users, and HIV-negative and HIV positive tobacco smokers. We measured six cytokines (TNF-α, IL-1β, IL-8, IL-6, IL-1ra, IL-10) and two chemokines (MCP-1 and RANTES). All were present in exosomes of healthy subjects, but their levels varied between different study groups. HIV-positive alcohol drinkers had higher levels of plasma IL-8 compared to those of HIV-positive non-drinkers. The IL-1ra level was significantly higher in exosomes of non-HIV-infected alcohol drinkers compared to those of HIV-positive alcohol drinkers. Interestingly, the IL-10 level was higher in exosomes compared with their respective plasma levels in all study groups except HIV-positive non-alcohol drinkers. IL-10 was completely packaged in exosomes of HIV-positive smokers. HIV-positive smokers had significantly higher levels of plasma IL-8 compared with HIV-positive non-smokers and significantly higher exosomal IL-6 levels compared with HIV-negative subjects. HIV-positive smokers had significantly increased plasma levels of IL-1ra compared to HIV-positive non-smokers. The MCP-1 levels in the plasma of HIV-positive smokers was significantly higher than in either HIV-positive non-drug abusers or HIV-negative smokers. Overall, the findings suggest that plasma cytokines and chemokines are packaged in exosomes at varying degrees in different study groups. Exosomal cytokines and chemokines are likely to have a significant biological role at distant sites including cells in the brain.

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Section: Discussionmentioning

confidence: 99%

Cytokine profiling of exosomes derived from the plasma of HIV-infected alcohol drinkers and cigarette smokers

et al. 2018

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“…This study further supports the importance of DAS to counteract CYP2E1-mediated metabolic toxicity. The distinct role of alcohol in contributing towards neurological/neurocognitive diseases, such as neuroAIDS [74, 108], concurrent with the role of CYP2E1 in brain alcohol metabolism further emphasizes the potential use of DAS as adjuvant therapy in treating these diseases effectively.…”

Section: Das: Protection Against Alcohol Analgesic Drugs and Othmentioning

confidence: 99%

Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1

Rao¹,

Midde²,

Miller³

et al. 2015

CDM

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Diallyl sulfide (DAS) and other organosulfur compounds are chief constituents of garlic. These compounds have many health benefits, as they are very efficient in detoxifying natural agents. Therefore, these compounds may be useful for prevention/treatment of cancers. However, DAS has shown appreciable allergic reactions and toxicity, as they can also affect normal cells. Thus their use as in the prevention and treatment of cancer is limited. DAS is a selective inhibitor of cytochrome P450 2E1 (CYP2E1), which is known to metabolize many xenobiotics including alcohol and analgesic drugs in the liver. CYP2E1-mediated alcohol/drug metabolism produce reactive oxygen species and reactive metabolites, which damage DNA, protein, and lipid membranes, subsequently causing liver damage. Several groups have shown that DAS is not only capable of inhibiting alcohol- and drug-mediated cellular toxicities, but also HIV protein- and diabetes-mediated toxicities by selectively inhibiting CYP2E1 in various cell types. However, due to known DAS toxicities, its use as a treatment modality for alcohol/drug- and HIV/diabetes-mediated toxicity have only limited clinical relevance. Therefore, effort is being made to generate DAS analogs, which are potent and selective inhibitor of CYP2E1 and poor substrate of CYP2E1. This review summarizes current advances in the field of DAS, its anticancer properties, role as a CYP2E1 inhibitor, preventing agent of cellular toxicities from alcohol, analgesic drugs, xenobiotics, as well as, from diseases like HIV and diabetes. Finally, this review also provides insights toward developing novel DAS analogues for chemical intervention of many disease conditions by targeting CYP2E1 enzyme.

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“…Several factors could explain synergic inflammation in HIV-HCV co-infection: both viruses can increase the permeability of the brain blood barrier and the expression of pro-inflammatory cytokines and chemokines, including IL-6 and IL-8. In addition, both can infect and replicate in microglia [27].…”

Section: Interpretation Of Resultsmentioning

confidence: 99%

Resting-state functional connectivity MRI analysis in Human Immunodeficiency Virus and Hepatitis C Virus co-infected subjects. A pilot study

Corgiolu

Barberini

Suri³

et al. 2018

European Journal of Radiology

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HIV-1, HCV and Alcohol in the CNS: Potential Interactions and Effects on Neuroinflammation

Cited by 20 publications

References 103 publications

Cytokine profiling of exosomes derived from the plasma of HIV-infected alcohol drinkers and cigarette smokers

Cytokine profiling of exosomes derived from the plasma of HIV-infected alcohol drinkers and cigarette smokers

Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1

Resting-state functional connectivity MRI analysis in Human Immunodeficiency Virus and Hepatitis C Virus co-infected subjects. A pilot study

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