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Immunomodulatory Properties of Kappa Opioids and Synthetic Cannabinoids in HIV-1 Neuropathogenesis

  • Shuxian Hu
  • Wen S. Sheng
  • Robert Bryan RockEmail author
INVITED REVIEW

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.

Keywords

HIV-1 Neuropathogenesis Cannabinoids Kappa opioid receptors 

Notes

Acknowledgments

We would like to thank Phillip K. Peterson for his significant scientific insight and counsel.

None of the authors has a commercial or other association that might pose a conflict of interest with the current review.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Shuxian Hu
    • 1
    • 2
  • Wen S. Sheng
    • 1
    • 2
  • Robert Bryan Rock
    • 1
    • 2
    • 3
    Email author
  1. 1.Center for Infectious Diseases and Microbiology Translational ResearchUniversity of Minnesota Medical SchoolMinneapolisUSA
  2. 2.Department of MedicineUniversity of Minnesota Medical SchoolMinneapolisUSA
  3. 3.Division of Infectious Diseases and International Medicine, Department of MedicineUniversity of Minnesota Medical SchoolMinneapolisUSA

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