# Cannabinoids Modulate Immune Cell-provoked Astrocyte Functions to Suppress HIV-Associated Neuroinflammatory Responses

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2022 · $488,022

## Abstract

PROJECT SUMMARY
An estimated 37 million people worldwide are infected with human immunodeficiency virus (HIV). Combined
antiretroviral therapy (ART) has turned HIV into a chronic infection with significantly longer life expectancy.
New health issues have surfaced as HIV patients live longer. Specifically, 50% of HIV-infected (HIV+)
individuals exhibit neurocognitive impairment, termed HIV-associated neurocognitive disorders (HAND). A key
event leading to HAND is persistent low-level chronic neuroinflammation resulting in neuronal damage and cell
death. A major contributor to HIV-induced neuroinflammation is activated monocytes, which are significantly
elevated in patients’ with HIV-associated dementia. Activated, CD16+ monocytes are infected by HIV in the
periphery and migrate across the blood-brain barrier (BBB) to release HIV virions and neurotoxic and
proinflammatory factors. Before entering the CNS, resting (CD16–) monocytes transition into the CD16+
through poorly understood mechanisms including elevated interferon alpha (IFNα), a potent antiviral cytokine
produced by plasmacytoid dendritic cells (pDC), an observation consistent with the IFNα gene signature in
monocytes from HIV patients. Chronic IFNα production in HIV patients has been linked to neurocognitive
impairment. In parallel, IFNα also activates CD8+ T cells, which are recruited from systemic circulation to cross
the BBB. Once in the perivascular space, activated monocytes and CD8+ T cells interact with astrocytes to
drive a chronic neuroinflammatory response leading to destruction of neurons and declining cognative function.
Interestingly, cannabis, which has constituents (e.g., Δ9-tetrahydrocannabinol (THC)) possessing immune
suppressive and anti-inflammatory activity, is widely used (approximately 25-37%) by HIV patients. The
beneficial vs. deleterious effects of cannabinoid therapy in HIV patients remains unknown and understudied.
Preliminary results show that THC suppresses IFNα-mediated CD16– to CD16+ monocyte transition as well as
IL-7 receptor upregulation on CD8+ T cells. Moreover, HIV+ marijuana-users (MJ+) have fewer circulating
CD16+ monocytes compared to HIV+MJ-. Preliminary data is also presented using a novel all human coculture
system demonstrating that both monocytes and CD8+ T cells, when cocultured with astrocytes significant drive
the secretion of astrocyte-derived inflammatory mediators, including IL-6 and IP-10, a response suppressed by
THC. Mechanistic studies are proposed to test the hypothesis: Cannabinoids suppress interferon-α-mediated
monocyte and CD8+ T cell activation in the periphery and their detrimental effects on astrocyte function, all of
which are key processes in HIV-associated chronic neuroinflammation.

## Key facts

- **NIH application ID:** 10152576
- **Project number:** 5R01DA047180-04
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Norbert E Kaminski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $488,022
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152576

## Citation

> US National Institutes of Health, RePORTER application 10152576, Cannabinoids Modulate Immune Cell-provoked Astrocyte Functions to Suppress HIV-Associated Neuroinflammatory Responses (5R01DA047180-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10152576. Licensed CC0.

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