Polymyxin B Attenuates LPS-Induced Death but Aggravates Radiation-Induced Death via TLR4-Myd88-IL-6 Pathway

• Main Authors: Ying Cheng, Jicong Du, Jiaqi Han, Weimin Sun, Fu Gao, Pei Zhang, Hainan Zhao, Ming Chen, Jianing Wang, Mingyu Wang, Suhe Dong, Ding Sun, Yandong Zhang, Jianguo Cui, Jianming Cai, Cong Liu
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2017-06-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Radiation; TLR4; Myd88; IL-6; Polymyxin B; LPS
• Online Access: http://www.karger.com/Article/FullText/478767
• ISSN: 1015-8987; 1421-9778

Background/Aims: Polymyxin B (PMB) is a cyclic cationic polypeptide antibiotic widely used to counteract the effects of endotoxin contamination, both in vitro and in vivo. Lipopolysaccharide (LPS) is an endotoxin that acts as a radiation protection factor. In this study, we focus on the role of PMB in LPS-induced and radiation-induced mortality in mice. Methods: Mice received total-body radiation or were pretreated by LPS or PMB, and the survival of mice was recorded. Elisa were used to detect the cytokines levels. Results: PMB decreased LPS-induced, but increased radiation-induced mortality in mice. Moreover, PMB could block the LPS-induced radioprotective effect. The ELISA and gene knock-out experiments indicated that PMB reduces TNF-α level to block LPS-induced mortality in mice, and inhibits IL-6, G-CSF and IL-10 to increase radiation-induced mortality via the TLR4-Myd88-IL-6 pathway. Conclusions: Our study revealed a role of PMB in LPS-induced endotoxemia and radiation exposure. We infer that the TLR4-Myd88-IL-6 pathway may play a crucial role in the process.