Tocilizumab alleviated lipopolysaccharide-induced acute lung injury by improving PI3K/AKT pathway.

Abstract

Acute lung injury (ALI) is a severe inflammatory condition of the respiratory system, associated with high morbidity and mortality. This study investigates the therapeutic potential of tocilizumab (TZ), an IL-6 receptor inhibitor, in mitigating lipopolysaccharide (LPS)-induced ALI by modulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. An ALI model was established using LPS induction. Lung damage was assessed by hematoxylin-eosin (H&E) staining, alongside measurements of respiratory function, including PaO₂/Fio₂ ratios, lung edema, airway resistance, and lung compliance. Western blotting analyzed the expression of phosphorylated PI3K and AKT (P-PI3K, P-AKT), while ELISA quantified levels of TNF-α, IL-1β, IL-6, and oxidative stress markers. Apoptosis was evaluated using the TUNEL assay, and key apoptotic proteins (Bcl-2, Bax, and caspase-3) were measured by Western blotting. The Cell Counting Kit-8 (CCK-8) assay was employed to determine cell viability. The LPS-induced model exhibited decreased P-PI3K and P-AKT levels, while TZ treatment significantly elevated these markers. TZ also reduced lung tissue damage, improved respiratory function, and decreased inflammation, oxidative stress, and apoptosis. However, co-administration with LY294002 (a PI3K inhibitor) blocked these benefits, reversing the protective effects of TZ. TZ alleviates lung injury and improves outcomes in LPS-induced ALI by enhancing the PI3K/AKT pathway.