Therapeutic Effect of Anti-FABP4 mAb (6H2) on Systemic Inflammation in Sepsis: Insights from Abdominal Organ Analysis

Sepsis is a life-threatening condition driven by dysregulated immune responses and multi-organ dysfunction, with limited treatments targeting its underlying pathophysiology. Growing evidence highlights fatty acid-binding protein 4 (FABP4) as a key mediator of inflammation and organ injury in sepsis. In this study, we investigated the therapeutic potential of an anti-FABP4 monoclonal antibody (6H2) in a murine endotoxemia model induced by lipopolysaccharide (LPS). Treatment with 6H2 significantly attenuated systemic inflammation, as evidenced by modulated leukocyte responses, and provided substantial tissue protection in the liver, lungs, kidneys, and heart, reducing histopathological damage. Our findings identify 6H2 as a promising novel therapeutic intervention for sepsis. Author SummaryTitleTherapeutic Potential of Anti-FABP4 Antibody (6H2) in Sepsis: Protection Against Systemic Inflammation and Organ Damage Key Findings- Sepsis, a life-threatening inflammatory condition, lacks targeted therapies. We investigated 6H2, a monoclonal antibody against fatty acid-binding protein 4 (FABP4), in a mouse model of sepsis. - 6H2 treatment significantly reduced sepsis severity, improved survival, and attenuated organ damage in the liver, lungs, kidneys, and heart. - Histopathological analysis revealed restored tissue integrity in 6H2-treated mice, with reduced inflammation and cell death compared to controls. - Complete Blood Count showed modulated immune responses, including altered leukocyte counts, suggesting 6H2s role in rebalancing inflammation. SignificanceFABP4 is a key driver of sepsis-related inflammation and organ dysfunction. Our study demonstrates that 6H2 not only mitigates systemic inflammation but also provides multi-organ protection, offering a promising therapeutic strategy for sepsis. These findings support further preclinical and clinical development of FABP4-targeted therapies.