The Anti-Inflammatory Effect of Cannabinoids on HIV-1-Infected Monocytes

The Human Immunodeficiency Virus, type 1 (HIV-1), is a human retrovirus that targets the host immune cells, inhibiting the immune response and incorporating itself into the genome of immune cells4. The number of estimated infections of HIV-1 worldwide is approximately 37 million people, predominantly in areas such as Sub-Saharan Africa, Southern Asia, and South America4. Currently, the treatment options mainly focus on combination Antiretroviral therapy (cART), which induces the virus into latency, resulting in undetectable levels of viral load. However, during latency, the HIV-1 infected cells continuously undergo low-level transcription4. This low-level transcription prompts residual viral particles to activate the NF-kB pathway, responsible for early regulation of the adaptive immune response, involving the production of cytokines and resulting in chronic inflammation of the central nervous system leading to HIV-associated neurocognitive disorder (HAND)3. During this experiment, the HIV-1-infected and uninfected monocyte cell lines U1 and U937, respectively, were treated with increasing concentrations of HU308 and CBD, both compounds have been shown to reduce inflammation in the CNS, likely due to the inhibition of NLRP3 inflammasome activity and thus reducing inflammatory cytokine release and pyroptosis1,2. Here we looked at the expression of NLRP3 inflammasome components and subsequent cytokine release, in both the whole cell extract and cell supernatants, derived from U1 HIV-1 infected cells after treatment with CBD and HU308. References: • Blevins, H. M., Xu, Y., Biby, S., & Zhang, S. (2022). The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases. Frontiers in aging neuroscience, 14, 879021. https://doi.org/10.3389/fnagi.2022.879021 • Dopkins, N., Miranda, K., Wilson, K., Holloman, B. L., Nagarkatti, P., & Nagarkatti, M. (2022). Effects of Orally Administered Cannabidiol on Neuroinflammation and Intestinal Inflammation in the Attenuation of Experimental Autoimmune Encephalomyelitis. Journal of neuroimmune pharmacology: the official journal of the Society on NeuroImmune Pharmacology, 17(1-2), 15–32. https://doi.org/10.1007/s11481-021-10023-6 • Mu, W., Patankar, V., Kitchen, S., & Zhen, A. (2024). Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection. Viruses, 16(2), 219. https://doi.org/10.3390/v16020219 • Ventura J. D. (2020). Human Immunodeficiency Virus 1 (HIV-1): Viral Latency, the Reservoir, and the Cure. The Yale journal of biology and medicine, 93(4), 549–560.