Immunomodulatory properties of kappa opioids and synthetic cannabinoids in HIV-1 neuropathogenesis

Shuxian Hu, Wen Sheng, R B Rock

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations

Abstract

Anti-retroviral therapy (ART) has had a tremendous impact on the clinical outcomes of HIV-1 infected individuals. While ART has produced many tangible benefits, chronic, long-term consequences of HIV infection have grown in importance. HIV-1-associated neurocognitive disorder (HAND) represents a collection of neurological syndromes that have a wide range of functional cognitive impairments. HAND remains a serious threat to AIDS patients, and there currently remains no specific therapy for the neurological manifestations of HIV-1. Based upon work in other models of neuroinflammation, kappa opioid receptors (KOR) and synthetic cannabinoids have emerged as having neuroprotective properties and the ability to dampen pro-inflammatory responses of glial cells; properties that may have a positive influence in HIV-1 neuropathogenesis. The ability of KOR ligands to inhibit HIV-1 production in human microglial cells and CD4 T lymphocytes, demonstrate neuroprotection, and dampen chemokine production in astrocytes provides encouraging data to suggest that KOR ligands may emerge as potential therapeutic agents in HIV neuropathogenesis. Based upon findings that synthetic cannabinoids inhibit HIV-1 expression in human microglia and suppress production of inflammatory mediators such as nitric oxide (NO) in human astrocytes, as well as a substantial literature demonstrating neuroprotective properties of cannabinoids in other systems, synthetic cannabinoids have also emerged as potential therapeutic agents in HIV neuropathogenesis. This review focuses on these two classes of compounds and describes the immunomodulatory and neuroprotective properties attributed to each in the context of HIV neuropathogenesis.

Original languageEnglish (US)
Pages (from-to)528-539
Number of pages12
JournalJournal of Neuroimmune Pharmacology
Volume6
Issue number4
DOIs
StatePublished - Dec 2011

Bibliographical note

Funding Information:
This work was supported, in part by U.S. Public Health Service grant DA025525 S.Hu.W.S.Sheng.R.B.Rock Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, Minneapolis, MN, USA

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

Keywords

  • Cannabinoids
  • HIV-1
  • Kappa opioid receptors
  • Neuropathogenesis

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