Marijuana May Quell HIV-Related Neuroinflammation via CD16 Expression
People with HIV who use marijuana have lower levels of two immune activation and inflammation markers than HIV-positive people who do not use marijuana, according to results of a cross-sectional comparison at Michigan State University.
Activated (CD16) monocytes probably contribute to neuroinflammation, while interferon-γ-inducible protein 10 (IP-10) provides a marker of neuroinflammation. Because a statistically significant proportion of people with HIV use marijuana, the research team conducted this study to gauge the impact of THC on percentage of monocytes expressing CD16, on monocyte production of IP-10, and on other processes.
Monocytes isolated from HIV-positive marijuana users could not induce CD16 expression when stimulated by interferon-alpha (IFN-α), whereas monocytes from HIV-positive and -negative nonusers could.
HIV-associated neurocognitive disorder (HAND) -- marked by damage to neurons -- remains prevalent in HIV populations despite viral control with antiretroviral therapy. Mechanisms underlying neuronal damage in people with HIV include chronic immune activation and central nervous system inflammation.
Researchers recruited HIV-positive men currently taking antiretrovirals. They determined marijuana use by self-report and serum detection of THC metabolites and divided men into marijuana users (HIV+MJ+) and nonusers (HIV+MJ-). They also recruited HIV-negative controls without detectable THC metabolites (HIV-MJ-). Isolating primary leukocytes from donor blood samples, the investigators used flow cytometry to measure levels of CD16 monocytes and IP-10. In donor peripheral blood mononuclear cells (PBMCs), they quantified the impact of THC and IFN-α stimulation on CD16 monocytes and IP-10.
The study involved 13 HIV+MJ+ men, 27 HIV+MJ- men, and 18 HIV-MJ- men. The HIV+MJ+ and HIV+MJ- groups were similar in age (mean about 53 years), HIV infection duration (mean 19.2 and 14.0 years), proportion with an undetectable viral load (76.9% and 86.2%), CD4 count (mean 500 and 610 cells/μL, P = 0.501), and body mass index (26 and 29.1 kg/m2, P = 0.136). Similar proportions of marijuana users and nonusers smoked cigarettes (30.8% and 31.0%) and drank alcohol (61.5% and 51.7%).
HIV+MJ+ men had significantly lower proportions of circulating CD16 (activated) monocytes than HIV+MJ- men (P = 0.026). Serum IP-10 concentrations also proved significantly lower in HIV+MJ+ men than in HIV+MJ- men (P = 0.005).
IFN-α treatment of PBMCs and purified monocytes significantly increased expression of CD16 in HIV+MJ- and HIV-MJ- men but not in HIV+MJ+ men, a result suggesting that marijuana may suppress monocyte induction of CD16. In addition, THC treatment of PBMCs and purified monocytes from HIV-MJ- men significantly decreased the percentage of CD16 monocytes in a concentration-dependent manner (P < 0.0003). Finally, THC treatment of PBMCs and purified monocytes significantly decreased IP-10 levels in all three study groups: HIV+MJ+, HIV+MJ-, and HIV-MJ-.
This study produced cell-based evidence that marijuana may modulate the pathway to neuroinflammation in people with HIV, a finding suggesting that cannabis may limit development of HAND. Specifically, the investigators found that male HIV-positive marijuana users have significantly lower levels of activated (CD16+) monocytes and lower concentrations of IP-10, an activation marker, than HIV-positive men who do not use marijuana. The small study could not use regression analysis to determine whether marijuana use or blood concentrations of THC metabolites independently predicted levels of CD16 monocytes or IP-10. But the 13 marijuana users and the 27 nonusers were similar in demographic, clinical, and behavioral factors.
Besides the small size of the study, the authors note other limitations: The analysis lacked an HIV-negative marijuana-user group; marijuana exposure could not be quantified in the HIV+MJ+ group; and the HIV-MJ- participants came from different geographical locations than the two HIV-positive groups. Finally, the study did not attempt to determine whether the better neuroinflammation profile in the HIV-positive marijuana users resulted in better neuropsychological test scores or lower HAND frequency.
The authors propose that "components of cannabis, including THC, may decelerate peripheral monocyte processes that are implicated in HIV-associated neuroinflammation." They suggest that "within the context of HIV-associated neuroinflammation and cognitive decline, cannabinoid therapies may decelerate peripheral immune processes that are implicated in HIV-associated neuroinflammation."