IL-37 Alleviates Sepsis-Induced Lung Injury by Inhibiting Inflammatory Response Through the TGF-β/Smad3 Pathway

Sepsis is caused by an uncontrolled inflammatory response and immune dysfunction, with lung injury being the most common complication and one of the leading causes of death in clinically ill patients. Interleukin 37 (IL-37) is a multifunctional cytokine that plays a vital role in various pathophysiological processes, including inflammation, infection, and immunity. The study involved both clinical and animal experiments (establishing an animal model of sepsis-induced lung injury). Firstly, 50 patients with sepsis-induced lung injury and 50 healthy controls were included. In addition, a more in-depth study was conducted using animal models. IL-37, IL-6, PCT, and CRP levels were significantly higher in the sepsis-induced lung injury group. Correlation analysis revealed that IL-37 significantly correlated with IL-6, PCT, and CRP levels. In animal experiments, IL-37 significantly attenuated CLP-induced pulmonary edema and cellular injury while reducing the levels of inflammatory factors IL-6 and TNF-α, as well as sepsis-related inflammatory markers PCT and CRP. Moreover, IL-37 significantly downregulated the expression levels of genes and proteins of apoptosis-related molecules Caspase-3 and Bax and pathway molecules TGF-β and Smad3. The TGF-β/Smad3 pathway is involved in the process of IL-37 inhibiting inflammatory response and ameliorating sepsis-induced lung injury.