Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice

• Published in: European journal of pharmacology 2024-05, Vol.971, p.176509-176509, Article 176509
• Main Authors: Mićanović, Dragica, Lazarević, Milica, Kulaš, Jelena, Despotović, Sanja, Stegnjaić, Goran, Jevtić, Bojan, Koprivica, Ivan, Mirkov, Ivana, Stanisavljević, Suzana, Nikolovski, Neda, Miljković, Đorđe, Saksida, Tamara
• Format: Article
• Language: English
• Subjects: ARDS; BALF; Ethyl pyruvate; HMGB1; Lung inflammation; poly(I:C)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2024.176509

Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic acid (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy. •EP treatment attenuates ARDS symptoms in poly(I:C)-treated mice.•Effector immune cells are less abundant in the DLN and lungs of EP-treated animals.•EP treatment reduces the expression and production of proinflammatory cytokines.•HMGB1 expression is downregulated in the lungs of EP-treated mice.