title: HIV-1 and alcohol: interactions in the central nervous system.
abstract: The use of alcohol has been associated with both an increased risk of acquisition of HIV-1 infection and an increased rate of disease progression among those already infected by the virus. The potential for alcohol to exacerbate the effects of HIV infection is especially important in the central nervous system (CNS) because this area is vulnerable to the combined effects of alcohol and HIV infection. The effects of alcohol on glial cells are mediated through receptors such as Toll-like receptor 4 and N-methyl-d-aspartate receptor. This causes the activation of signaling molecules such as interleukin-1 receptor-associated kinase and various members of the P38 mitogen-activated protein kinase family and subsequent activation of transcription factors such as nuclear factor-kappa beta and activator protein 1. The eventual outcome is an increase in pro-inflammatory cytokine production by glial cells. Alcohol also induces higher levels of NADPH oxidase in glial cells, which leads to an increased production of reactive oxygen species (ROS). Viral invasion of the CNS occurs early after infection, and HIV proteins have also been demonstrated to increase levels of pro-inflammatory cytokines and ROS in glial cells through activation of some of the same pathways activated by alcohol. Both cell culture systems and animal models have demonstrated that concomitant exposure to alcohol and HIV/HIV proteins results in increased levels of expression of pro-inflammatory cytokines such as interleukin-1 beta and tumor necrosis factor-alpha, along with increased levels of oxidative stress. Clinical studies also suggest that alcohol exacerbates the CNS effects of HIV-1 infection. This review focuses on the mechanisms by which alcohol causes increased CNS damage in HIV-1 infection.
authors.affiliation: Division of Pharmacology and Toxicology , School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Silverstein
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D002490:Central Nervous System / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D000431:Ethanol; D015658:HIV Infections / Q000503:physiopathology*; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D054298:Human Immunodeficiency Virus Proteins / Q000502:physiology; D006801:Humans
chemical_list: D054298:Human Immunodeficiency Virus Proteins; D000431:Ethanol
keywords: Alcohol; Central Nervous System; HIV-1