Virginia Commonwealth University Richmond, Virginia, United States
Background: Opioids intrinsically alter the course of HIV infection and accelerate HIV-associated neurocognitive disorders (HAND)1 despite effective antiretroviral therapy. The neuroinflammatory impacts of fentanyl on HAND remain largely unknown. We examined the interplay of fentanyl and HIV on inflammatory chemokines in the brain. Methods: This experimental study used the Tat-transgenic mouse model, an established model of HAND. Fifteen Tat+ and 15 Tat- mice were randomly assigned to receive fentanyl or placebo subcutaneously for 7 days. Brain chemokine levels were measured using a LegendPlex Chemokine kit. Results: A 3-WAY ANOVA revealed significant interactions between regions and fentanyl exposure on chemokines involved in HIV suppression, monocyte migration, and cytokine secretion2. In the striatum and hippocampus, fentanyl increased CCL4 and decreased CCL3 for both Tat groups. There were no significant differences in CCL11 in the striatum or hippocampus for any group. Conclusion: This study presents the novel findings that in the striatum, fentanyl alters chemokines irrespective of Tat, and in the hippocampus, chemokine alterations differed between Tat- and Tat+ mice. Additional research will explore interactions between fentanyl and HIV in an infectious model, and HIV therapies.
1. Saylor D, Dickens AM, Sacktor N, et al. HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment. Nat Rev Neurol. 2016;12(4):234-248. doi:10.1038/nrneurol.2016.27 2. Sindhu, Kochumon, Shenouda, Wilson, Al-Mulla, Ahmad. The Cooperative Induction of CCL4 in Human Monocytic Cells by TNF-α and Palmitate Requires MyD88 and Involves MAPK/NF-κB Signaling Pathways. IJMS. 2019;20(18):4658. doi:10.3390/ijms20184658
