Opioids, astroglial chemokines, microglial reactivity, and neuronal injury in HIV-1 encephalitis
Book Chapter
Hauser, KF, El-Hage, N, Bruce-Keller, AJ et al. (2010). Opioids, astroglial chemokines, microglial reactivity, and neuronal injury in HIV-1 encephalitis
. 353-377. 10.1007/978-1-4419-0793-6_16
Hauser, KF, El-Hage, N, Bruce-Keller, AJ et al. (2010). Opioids, astroglial chemokines, microglial reactivity, and neuronal injury in HIV-1 encephalitis
. 353-377. 10.1007/978-1-4419-0793-6_16
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.
