Aerosolized adenoviral IL4/IL10 delivery alleviates LPS-induced acute lung injury

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung diseases with high morbidity and mortality, lacking specific treatments. Inhalation offers direct access to the damaged lung epithelium, making tracheal gene delivery a promising approach. However, challenges such as low efficiency, off-target effects, and repeated dosing limit its effectiveness. In this study, we developed an inhalable recombinant adenoviral vector (Ad-IL4/10) carrying dual reporter genes to deliver interleukin-10 (IL10) and interleukin-4 (IL4) to the lungs, enabling efficient and sustained expression of anti-inflammatory cytokines. Using a lipopolysaccharide (LPS)-induced lung injury mouse model, the anti-inflammatory effects of aerosolized Ad-IL4/10 were evaluated. The results showed that aerosolized Ad-IL4/10 significantly reduced weight loss, lung wet-to-dry weight ratio, and total protein levels in bronchoalveolar lavage fluid (BALF). Additionally, it alleviated pulmonary inflammation and alveolar damage while suppressing proinflammatory markers and LPS-induced monocyte and neutrophil infiltration. Ad-IL4/10 also restored monocyte-macrophage homeostasis. These findings indicate that an inhalable adenoviral vector effectively mitigates LPS-induced lung injury through IL4 and IL10 delivery, offering a promising therapeutic strategy for ALI.