Effects of dexmedetomidine on early and late cytokines during polymicrobial sepsis in mice
- 666 Downloads
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-α (TNF-α) and interlukin-6 (IL-6)] and high mobility group box 1 (HMGB1).
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-α, 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.
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-α 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).
Dexmedetomidine could reduce the mortality rate and inhibit pro-inflammatory cytokine responses during polymicrobial sepsis in mice.
KeywordsDexmedetomidine Sepsis HMGB1 TNF-α IL-6
- 6.Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2008;34:17–60.PubMedCrossRefGoogle Scholar
- 7.Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A, Tracey KJ. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285:248–51.PubMedCrossRefGoogle Scholar
- 10.Ueno H, Matsuda T, Hashimoto S, Amaya F, Kitamura Y, Tanaka M, Kobayashi A, Maruyama I, Yamada S, Hasegawa N, Soejima J, Koh H, Ishizaka A. Contributions of high mobility group box protein in experimental and clinical acute lung injury. Am J Respir Crit Care Med. 2004;170:1310–6.PubMedCrossRefGoogle Scholar
- 14.Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C, Vedio A, Singer M, Feneck R, Treacher D, Willatts SM, Grounds RM. Preliminary UK experience of dexmedetomidine a novel agent for postoperative sedation in the intensive care unit. Anaesthesia. 1999;54:1136–42.PubMedCrossRefGoogle Scholar
- 15.Bachand RT, List W, Etropolski M, Martin E. A phase III study evaluating dexmedetomidine for sedation in postoperative patients. Anesthesiology. 1999;91:A296.Google Scholar
- 16.Triltsch AE, Welte M, von Homeyer P, Grosse J, Genähr A, Moshirzadeh M, Sidiropoulos A, Konertz W, Kox WJ, Spies CD. Bispectral index-guided sedation with dexmedetomidine in intensive care: a prospective, randomized, double blind, placebocontrolled phase II study. Crit Care Med. 2002;30:1007–14.PubMedCrossRefGoogle Scholar
- 21.Otero-Antón E, González-Quintela A, López-Soto A, López-Ben S, Llovo J, Pérez LF. Cecal ligation and puncture as a model of sepsis in the rat: influence of the puncture size on mortality, bacteremia, endotoxemia and tumor necrosis factor alpha levels. Eur Surg Res. 2001;33:77–9.PubMedCrossRefGoogle Scholar
- 22.Heuer JG, Bailey DL, Sharma GR, Zhang T, Ding C, Ford A, Stephens EJ, Holmes KC, Grubbs RL, Fynboe KA, Chen YF, Jakubowski JA. Cecal ligation and puncture with total parenteral nutrition: a clinically relevant model of the metabolic, hormonal, and inflammatory dysfunction associated with critical illness. J Surg Res. 2004;121:178–86.PubMedCrossRefGoogle Scholar
- 33.Wakabayashi G, Gelfard JA, Jung WK, Connolly RJ, Burke JF, Dinarello CA. Staphylococcus epidermids induces complement activation, tumor necrosis factor and interleukin-1, a shock like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coil. J Clin Invest. 1991;87:1925–35.PubMedCrossRefGoogle Scholar
- 46.Shao YM, Yao HG, Liang XZ, Xia YH. Relation between level of expression of high mobility group protein B1 in hepatic tissue with the severity and prognosis of sepsis in rats. Chin Crit Care Med. 2006;18:668–72.Google Scholar