Exploring ozanimod’s role in reducing lung inflammation in a bacterial ARDS model 2582

Description Acute respiratory distress syndrome (ARDS) is a severe complication of infections like bacterial and viral pneumonia, characterized by increased vascular permeability and a heightened cytokine response. While prophylactic use of sphingosine-1-phosphate receptor 1 (S1P1) ligands has shown protective effects in mice against lethal influenza virus exposure by limiting endothelial overactivation, permeability, and cytokine amplification, current knowledge remains largely limited to prophylactic models of ARDS, primarily related to viral infections. Given that bacterial ARDS is prevalent and has a high mortality rate (≈35%), identifying new therapeutic interventions is critical. Here, we used a Streptococcus pneumoniae-induced ARDS model in mice to evaluate whether the S1P1 ligand ozanimod could serve as a viable therapeutic option in bacterial ARDS. Mice were inoculated with S. pneumoniae and treated 24 hours later with antibiotics, with or without ozanimod. This model mimics the progression to ARDS that continues to worsen despite effective antibiotic therapy. Ozanimod treatment accelerated recovery, evidenced by faster weight gain post-infection, and tended to reduce both lung edema (wet lung weight) and neutrophil counts in bronchoalveolar lavage fluid. Ozanimod also significantly reduced CD69 levels on lung lymphocytes. These results suggest that S1P1 targeting may offer therapeutic benefits in bacterial ARDS.