AUTHOR=Liu Menglin , Wang Zhen , Zhang Jishou , Ye Di , Wang Menglong , Xu Yao , Zhao Mengmeng , Feng Yongqi , Lu Xiyi , Pan Heng , Pan Wei , Wei Cheng , Tian Dan , Li Wenqiang , Lyu Jingjun , Ye Jing , Wan Jun 

TITLE=IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.950029

DOI=10.3389/fcvm.2022.950029

ISSN=2297-055X

ABSTRACT=Background
Cardiac dysfunction is one of the most common complications of sepsis and is associated with the adverse outcomes and high mortality of sepsis patients. IL-12p40, the common subunit of IL-12 and IL-23, has been shown to be involved in a variety of inflammation-related diseases, such as psoriasis and inflammatory bowel disease. However, the role of IL-12p40 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains obscure. This study aimed to explore the role of IL-12p40 in LPS-induced cardiac dysfunction and its potential mechanisms.
Methods
In this study, mice were treated with LPS and the cardiac expression of IL-12p40 was determined. Then, IL-12p40-/- mice were used to detect the role and mechanisms of IL-12p40 in LPS-induced cardiac injury. In addition, monocytes were adoptively transferred to IL-12p40-/- mice to explore their effects on LPS-induced cardiac dysfunction. 
Results
The results showed that cardiac IL-12p40 expression was significantly increased after treatment with LPS. In addition, IL-12p40 deletion significantly aggravated LPS-induced cardiac dysfunction, as evidenced by the increased serum levels of cardiomyocyte injury markers and deteriorated cardiac function. Moreover, IL-12p40 deletion enhanced LPS-induced monocyte accumulation and cardiac expression of inflammatory cytokines and increased the phosphorylation levels of p65 (p-p65). Furthermore, adoptive transfer WT mouse monocytes to IL-12p40-/- mice alleviated LPS-induced cardiac dysfunction.
Conclusion
IL-12p40 deletion significantly aggravated LPS-induced cardiac injury and cardiac dysfunction in mice by regulating the NF-κB signalling pathway, and this process was related to monocytes. Therefore, IL-12p40 may be an attractive target for sepsis-induced cardiac dysfunction.