Clioquinol improves Sepsis-induced immunosuppression and enhances host anti-infective defense by restoring macrophage...

Sepsis-induced immunosuppression is a core factor contributing to opportunistic infections and high mortality in patients, with macrophage phagocytic dysfunction being a critical component. Currently, effective therapeutic approaches to reverse macrophage phagocytic capacity remain limited.

The study employed an endotoxin-tolerant (ET) macrophage model and a mouse sepsis model induced by cecal ligation and perforation (CLP). The effects of clioquinol (ClioQ) on macrophage phagocytic function, inflammatory cytokine expression, and in vitro/in vivo clearance of fungi (Candida albicans, C. albicans) and bacteria (Escherichia coli, E. coli) were evaluated via flow cytometry-assessed phagocytosis, organ pathogen burden detection, and histopathological analysis.

In the ET model, ClioQ treatment not only restored TNF-α secretion in response to lipopolysaccharide stimulation but also significantly rescued impaired phagocytosis and intracellular bactericidal functions. In the CLP-induced macrophage phagocytosis impairment model, ClioQ effectively improved macrophage phagocytosis of C. albicans and E. coli at non-antifungal pharmacological doses. In a secondary fungal infection model following CLP-induced sepsis, ClioQ (6 mg/kg) treatment significantly enhanced macrophage clearance efficiency against pathogens and markedly improved host survival.

ClioQ was identified as a potential immunomodulator that enhances host defense capabilities by directly repairing phagocytic dysfunction in macrophages during the immunosuppressive phase of sepsis. This approach significantly improves organ injury and increases survival rates, offering a novel candidate strategy for immune-adjuvant therapy in sepsis.