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Muramyl Dipeptide Enhances Thermal Injury–Induced Inflammatory Cytokine Production and Organ Function Injury in Rats

Liang, Hui*; Song, Xue-Min*; Wu, Xiao-Jing; Li, Jian-Guo*; Han, Yi*; Wang, Yan-Lin*; Li, Hui*; Zhang, Zong-Ze*; Le, Lin-Li*; Xu, Yang*

doi: 10.1097/SHK.0000000000000164
Basic Science Aspects

ABSTRACT The bacterial infection following thermal injury is a very important factor of excessive inflammatory response and multiple organ damage. Muramyl dipeptide (MDP) is the key structure of gram-positive bacteria and gram-negative bacteria triggering the innate immune system. The aim of the present study was to determine the effect of MDP on thermal injury–induced inflammatory responses, organ function injury, and mortality in rats. Fifty male Sprague-Dawlay rats were randomly divided into three groups: normal control group, scald group, and MDP group. Scald group only suffered 20% total body surface area third-degree thermal injury. Muramyl dipeptide 5 mg·kg−1 was administered through the femoral vein at 24 h after thermal injury in the MDP group. Plasma inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay. An additional 90 male Sprague-Dawley rats were randomly divided into three groups to observe the survival rate in 72 h. Plasma levels of interleukin-6, interleukin-10, interferon-γ, and high-mobility group box 1; the white blood cell counts; the serum concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatine kinase isoenzyme-MB, blood urea nitrogen, and creatinine; and the activity of lung tissue myeloperoxidase significantly increased after thermal injury alone. Compared with the scald group, MDP led to more serious inflammatory responses and organ function damage and higher mortality (P < 0.05, respectively). These data indicate that MDP exacerbates thermal injury–induced inflammatory cytokine production, accompanied by multiple organ dysfunction syndrome and high mortality in rats.

*The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Wuchang; and Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Wuchang, Hubei Province, China

Received 14 Nov 2013; first review completed 4 Dec 2013; accepted in final form 28 Feb 2014

Address reprint requests to Xue-Min Song, MD, Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei Province, China. E-mail:

This study was supported by the National Natural Science Foundation of China (grant no. 81101449), by the Central University Special Foundation in Basic Research (grant no. 111058), and by the Natural Science Foundation of Hubei Province of China (grant no. 2010CDB00404).

© 2014 by the Shock Society