Effects of dexmedetomidine on early and late cytokines during polymicrobial sepsis in mice
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Inflammation Research
ORIGINAL RESEARCH PAPER
Effects of dexmedetomidine on early and late cytokines during polymicrobial sepsis in mice Li Xu • Hongguang Bao • Yanna Si Xiaoliang Wang
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Received: 24 March 2012 / Revised: 18 January 2013 / Accepted: 8 February 2013 / Published online: 5 March 2013 Ó Springer Basel 2013
Abstract Objective We investigated whether dexmedetomidine provided protective effects on cecal ligation and puncture (CLP)–induced septic mice, through suppressing the expression of pro-inflammatory cytokines [tumor necrosis factor-a (TNF-a) and interlukin-6 (IL-6)] and high mobility group box 1 (HMGB1). Methods The model of sepsis was set up by CLP in 136 male BALB/c mice (40 mice for survival studies and 96 for cytokine studies) which were divided into four groups, including a C, CLP, DEX ? CLP and CLP ? DEX group. The serum levels of TNF-a, IL-6 and HMGB1 were detected at 6, 12, 24 and 48 h after operations, and lung HMGB1 mRNA were analyzed at 24 and 48 h. The mortality rates were calculated 7 days after the operations. Results The mortality rates 7 days after operations were significantly lower in the CLP ? DEX (50 %) and DEX ? CLP (30 %) groups than in the CLP group (90 %). Serum concentrations of IL-6 and TNF-a decreased significantly in dexmedetomidine administration groups compared with the CLP group. The levels of HMGB1 and lung HMGB1 mRNA were lower in the dexmedetomidine administration groups than in the CLP group. There was a significant correlation between lung HMGB1 mRNA and serum HMGB1(r = 0.858). Conclusions Dexmedetomidine could reduce the mortality rate and inhibit pro-inflammatory cytokine responses during polymicrobial sepsis in mice.
Responsible Editor: Artur Bauhofer. L. Xu H. Bao (&) Y. Si X. Wang Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China e-mail: [email protected]
Keywords Dexmedetomidine Sepsis HMGB1 TNF-a IL-6
Introduction Sepsis and septic shock are common and fatal disorders, representing the major determinant of morbidity and mortality in intensive care units [1]. The cascade of sepsis may proceed to the development of one or multiple organ dysfunctions, accompanied by other conditions such as disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS) [1–3]. Over the last decade, the treatment of sepsis focused on cytokine block, such as tumor necrosis factor-a (TNF-a) antibody, transcription factor (TF) inhibitor and nitric oxide (NO) inhibitors, except for anti-inflammatory strategies and volume resuscitation [3–6]. However, the efficiency of these strategies remains controversial requiring further studies, and sepsis continues to be associated with high morbidity and mortality in clinical practice. Consequently, we must explore a new therapeutic intervention to deal with the septic syndrome. As a DNA-binding highly conserved protein, highmobility group box protein 1 (HMGB1) is abundantly present in cytoplasm and nuclei, which maintains nu
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