Opioids, Astroglial Chemokines, Microglial Reactivity, and Neuronal Injury in HIV-1 Encephalitis

  • Kurt F. Hauser
  • Nazira El-Hage
  • Annadora J. Bruce-Keller
  • Pamela E. Knapp


The interrelatedness of opioids, chemokines, and glia are revealed in the molecular mechanisms underlying the exaggerated comorbidity seen in the CNS of HIV-infected individuals who abuse opioids. Opioid drugs exacerbate the inflammatory and neurodegenerative effects of HIV-1 through actions on µ opioid receptor (MOP) expressing astrocytes by unbalancing ion homeostasis, which potentiates chemokine release and establishes intercellular inflammatory cascades involving orchestrated production of CCL5 and CCL2. Convergent opioid-HIV signals synergistically disrupt ion and oxidative homeostasis in astrocytes, initiating opiate-driven, astroglial-derived proinflammatory cascade leading to massive chemokine release. Exaggerated macrophage recruitment/microglial overactivation combined with the potentiation of oxidative and nitrosative stress in macrophages/microglia by opioids further fuels and escalates CNS injury. Thus, opioid abuse intensifies HIV encephalitis by short-circuiting the neuroprotective effects of astroglia and by potentiating spiraling proinflammatory cascades involving astroglial-derived chemokines.


Opioid Receptor Chemokine Release Cellular Toxin Paradoxical Reduction Glial Type 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We gratefully acknowledge the support of the National Institute on Drug Abuse grant DA P01 19398.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Kurt F. Hauser
    • 1
  • Nazira El-Hage
    • 1
  • Annadora J. Bruce-Keller
    • 1
  • Pamela E. Knapp
    • 1
  1. 1.Department of Pharmacology and ToxicologyVirginia Commonwealth University School of MedicineRichmondUSA

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