Postdoctoral Fellow University of South Carolina Columbia, South Carolina, United States
Disclosure(s):
Shruthi Thada, PhD: No financial relationships to disclose
Introduction/Rationale: Acute Respiratory Distress Syndrome (ARDS) is a severe inflammatory lung disorder associated with high mortality. Currently, there are no FDA-approved pharmaceuticals approved for treatment of this disorder. This study evaluated the therapeutic potential of Δ8-Tetrahydrocannabinol (Δ8-THC), a cannabinoid that is less psychoactive than Δ9-THC, in a murine model of LPS-induced ARDS.
Methods: Female C57BL/6 mice received LPS (10 mg/kg, intratracheally) to induce ARDS, followed by Δ8-THC or vehicle treatment (i.p.). After 48h, lung tissue was collected for scRNA-seq analysis.
Results: scRNA-seq analysis of vehicle & Δ8-THC treated lungs identified sixteen transcriptionally dis-tinct clusters across stromal, endothelial, myeloid, and lymphoid lineages. Δ8-THC significantly reduced infiltration of neutrophils, while increasing the populations of polymorphonuclear MDSCs, immune endothelial cells and macrophages compared to vehicle. Neutrophil clusters from vehicle group showed enrichment of ribosomal and translational activity reflecting inflammatory stress which were significantly downregulated in Δ8-THC treated group, and instead shifted gene expression toward interferon-responsive, immunoregulatory programs. Δ8-THC-enriched clusters exhibited increased interactions via COLLAGEN, APP, CypA and CDH5 pathways, consistent with enhanced endothelial stabilization.
Conclusion: Δ8-THC alleviated lung inflammation in LPS-induced ARDS by reprogramming immune and endothelial responses toward interferon-driven, regulatory states. These findings suggest a potential therapeutic role for Δ8-THC in restoring lung homeostasis during ARDS.
