Staphylococcal Enterotoxin B (SEB) and Cannabidiol (CBD) effect evaluation on alveolar macrophage functioning in Acute Respiratory Distress Syndrome (ARDS) 3921

Description Acute Respiratory Distress Syndrome (ARDS) is a severe inflammatory condition with high mortality, affecting about 200,000 individuals annually in the US. Alveolar macrophages play a critical role in ARDS by regulating inflammation, phagocytosis, and tissue repair. This study investigates cannabidiol (CBD), a non-psychoactive cannabis derivative, as a potential modulator of macrophage dysfunction caused by staphylococcal enterotoxin B (SEB), a superantigen associated with toxic shock and pulmonary inflammation. Our Single-cell RNAseq data shows that CBD significantly alters macrophage infiltration and functional signaling. Using the MH-S alveolar macrophage cell line and flow cytometry, we assessed phagocytosis, efferocytosis, apoptosis, and lipid metabolism after treatments with SEB and CBD, both alone and in combination. Results indicate CBD restores phagocytic activity to near-normal levels, reduces lipid peroxidation, and promotes efferocytosis, highlighting improved tissue homeostasis. In vivo, analyses revealed that CBD enhances phagocytic activity compared to SEB alone and continues to reduce apoptosis in both alveolar and interstitial macrophages. The prevention of apoptosis in alveolar macrophages suggests CBD protects against SEB-induced DNA damage. These findings suggest CBD’s potential to restore immune balance and protect against cellular damage in ARDS and other diseases, presenting a range of therapeutic benefits. Funding Sources Supported by NIH grant R00GM147910 to KW Topic Categories Immune Mechanisms of Human Disease (HUM)