Mild Hypothermia Alleviates CLP-induced Multiple Organ Dysfunction by Mitigating Pyroptosis Through the TLR4/NF-κB/NLRP3 Signaling Pathway

Abstract

Multiple organ failure secondary to severe sepsis leads to increased morbidity and mortality and is often accompanied by inflammation and immune system dysfunction. Mild hypothermia has been shown to have anti-inflammatory properties, but whether it can exert a protective effect in cases of multiple organ failure remains unclear. Thus, in this study, we investigated the protective effect of mild hypothermia on septic multiple organ failure and the underlying mechanism for this effect. Sepsis was induced through the cecal ligation and puncture (CLP) method. Rats were then housed at normal (36-38°C) or mild hypothermic (32-34°C) temperature for 10 h. CLP-induced effects on inflammatory cytokines and biochemical markers in serum were reversed by mild hypothermia. The pathological injury score and the expressions of pyroptosis markers, including TLR4, MyD88 and NF-κB signaling molecules, showed a similar trend. Moreover, 3 d survival of CLP rats was improved by mild hypothermia. Mild hypothermia alleviated CLP-induced organ failure and the downstream effects on pyroptosis, probably through the TLR4/NF-κB/NLRP3 signaling pathway.