Hydrogen mitigates acute lung injury through upregulation of M2 and downregulation of M1 macrophage phenotypes

Objectives: Acute lung injury (ALI) is still a leading cause of morbidity and mortality in critically ill patients. ALI can be induced by sepsis, ventilator, hyperoxia, and ischemia-reperfusion. In the management of ALI, studies have shown that low concentration hydrogen has a therapeutic effect on acute lung injury. The present study was designed to investigate the effects and corresponding mechanism of the inhalation of hydrogen on ALI. Methods: C57 male mice underwent intraperitoneal injection of lipopolysccharide (LPS) to induce sepsis. Then, the mice were given 2% hydrogen. The survival rate, lung injury, inflammatory factors and macrophage phenotypic changes were assessed in bronchoalveolar lavage fluid (BALF). In vitro experiment, we obtained primary mouse bone marrow-derived macrophages (BMDM) incubated by LPS to explore the anti-inflammatory effects and corresponding mechanism. Results: Treatment with 2% hydrogen showed a substantial attenuation of inflammations, adverse lung histopathological changes and decreased M1 macrophage phenotypes while increased M2 macrophage phenotypes. Importantly, the decreased M1 macrophage phenotypes while increased M2 macrophage phenotypes were observed in LPS-stimulated macrophages treated with 2% hydrogen. Further, we observed significantly low levels of TNF alpha in LPS-induced macrophages treated with 2% hydrogen. The effects were ascribed to an inhibition of phosphorylation of p38 MAPK. Conclusion: 2% hydrogen may reduce sepsis-induced inflammatory responses in animals and in macrophages, and the inhibition to the activation of the MAPK/TNF-alpha may contribute to this protection.