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Published on: September 19, 2010
Phenotypic changes in the brain of SIV-infected macaques exposed to methamphetamine parallel macrophage activation
Nikki Bortell1, Brenda Morsey2, Liana Basova1
1Department of Molecular and Cellular Neurosciences, The Scripps Research Institute La Jolla, CA, USA.
Abstract:
One factor in the development of neuroAIDS is the increase in the migration of pro-inflammatory CD8 T cells across the blood-brain barrier. Typically these cells are involved with keeping the viral load down. However, the persistence of above average numbers of CD8 T cells in the brain, not necessarily specific to viral peptides, is facilitated by the upregulation of IL15 from astrocytes, in the absence of IL2, in the brain environment. Both IL15 and IL2 are common gamma chain (γc) cytokines. Here, using the non-human primate model of neuroAIDS, we have demonstrated that exposure to methamphetamine, a powerful illicit drug that has been associated with HIV exposure and neuroAIDS severity, can cause an increase in molecules of the γc system. Among these molecules, IL15, which is upregulated in astrocytes by methamphetamine, and that induces the proliferation of T cells, may also be involved in driving an inflammatory phenotype in innate immune cells of the brain. Therefore, methamphetamine and IL15 may be critical in the development and aggravation of central nervous system immune-mediated inflammatory pathology in HIV-infected drug abusers.
Insights
Methamphetamine exposure increases common gamma chain cytokines like IL15 in the brain, potentially worsening neuroinflammation in HIV-infected individuals. This drug may drive central nervous system immune pathology in neuroAIDS.
Area of Science:
- Neuroimmunology
- Neurovirology
- Pharmacology
Background:
- NeuroAIDS involves increased pro-inflammatory CD8 T cell migration into the brain.
- Astrocytes upregulate IL15 (a common gamma chain cytokine) in the brain, promoting T cell persistence.
- IL15 and IL2 are key common gamma chain (γc) cytokines involved in immune responses.
Purpose of the Study:
- To investigate the impact of methamphetamine exposure on the common gamma chain (γc) cytokine system in a non-human primate model of neuroAIDS.
- To determine if methamphetamine influences IL15 levels in astrocytes and T cell proliferation within the brain.
Main Methods:
- Utilized a non-human primate model relevant to neuroAIDS.
- Assessed the effects of methamphetamine exposure on γc system molecules, including IL15.
- Examined IL15 upregulation in astrocytes and its potential role in T cell proliferation and innate immune cell activation.
Main Results:
- Methamphetamine exposure led to an increase in molecules of the γc system.
- Methamphetamine upregulated IL15 in astrocytes.
- Upregulated IL15 may drive T cell proliferation and contribute to inflammation in brain innate immune cells.
Conclusions:
- Methamphetamine and IL15 may play critical roles in the development and exacerbation of central nervous system immune-mediated inflammatory pathology.
- These findings are particularly relevant for HIV-infected drug abusers experiencing neuroAIDS.
- Understanding these interactions is crucial for managing neuroinflammation in neuroAIDS.
