The impact of cannabinoids on inflammasome signaling in HIV-1 infection

NeuroImmune Pharmacology and Therapeutics

“Human immunodeficiency virus type 1 (HIV-1) is a chronic disease that afflicts over 38 million people worldwide without a known cure. The advent of effective antiretroviral therapies (ART) has significantly decreased the morbidity and mortality associated with HIV-1 infection in people living with HIV-1 (PWH), thanks to durable virologic suppression. Despite this, people with HIV-1 experience chronic inflammation associated with co-morbidities. While no single known mechanism accounts for chronic inflammation, there is significant evidence to support the role of the NLRP3 inflammasome as a key driver.

Numerous studies have demonstrated therapeutic impact of cannabinoids, including exerting modulatory effects on the NLRP3 inflammasome. Given the high rates of cannabinoid use in PWH, it is of great interest to understand the intersecting biology of the role of cannabinoids in HIV-1-associated inflammasome signaling. Here we describe the literature of chronic inflammation in people with HIV, the therapeutic impact of cannabinoids in PWH, endocannabinoids in inflammation, and HIV-1-associated inflammation. We describe a key interaction between cannabinoids, the NLRP3 inflammasome, and HIV-1 viral infection, which supports further investigation of the critical role of cannabinoids in HIV-1 infection and inflammasome signaling.”

“It is evident from the literature that cannabinoids show protective effects against inflammation associated with HIV-1. In both human and animal studies, THC/cannabis treatment has been shown to reduce inflammatory markers, including NLRP3-associated cytokine signaling and T-cell activation and proliferation. Studies also implicate a neuroprotective effect against NO-mediated cytotoxicity and BBB breakdown in rodents. Taken together, these findings suggest a role for cannabinoid receptor activation in reducing chronic inflammation and associated pathologies in PWH.”

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