Protective effect of Secukinumab on severe sepsis model rats by neutralizing IL-17A to inhibit IKBα/NFκB inflammatory signal pathway

Abstract

Abstract Secukinumab is a specific neutralizing antibody for IL-17A. At present, numerous studies have confirmed the important role of IL-17A in sepsis, but the role of secukinumab in sepsis has not been studied. The present study explored the protective effect and underlying mechanism of secukinumab in severe sepsis model rats. We established a severe sepsis rat model using cecal ligation and puncture (CLP). The optimal dose of secukinumab was determined by observing the 7-day survival rate of severe sepsis model rats. The expression levels of TNF-α, IL-6, and IL-17A in plasma and lung tissue were determined by enzyme-linked immunosorbent assay. The degree of pathological damage to lung tissue was evaluated by hematoxylin–eosin (H–E) staining and pathological damage scale. The expressions of IKBα/NFκB pathway proteins and downstream-related inflammatory factors were detected by western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). Our results show that high-dose secukinumab can inhibit the activation of the IKBα/NFκB inflammatory pathway by neutralizing IL-17A and reducing the gene expression of pathway-related inflammatory cytokines, thereby reducing the levels of inflammatory cytokines in lung tissue and plasma, thereby reducing the damage of lung tissue in severe sepsis model rats and improving the systemic inflammatory response.

Keywords

• Secukinumab
• Sepsis
• Acute lung injury
• IL-17A
• Inflammatory pathway