High HMGB1 level is associated with poor outcome of septicemic melioidosis
High HMGB1 level is associated with poor outcome of septicemic melioidosis
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DOI：
10.1016/j.ijid.2014.07.025
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发表时间：
2014-11-01
影响因子：
8.4
通讯作者：
Wongratanacheewin, Surasakdi
中科院分区：
文献类型：
--
作者：
Charoensup, Jaruek;Sermswan, Rasana W.;Wongratanacheewin, Surasakdi
目的：高水平的HMGB 1（高迁移率族蛋白1）-一种迟发性炎症介质-是几种感染性疾病中致命败血症的标志物。研究类鼻疽伯克霍尔德氏菌感染患者血浆中HMGB 1的水平以及疾病的严重程度。方法：检测77例脓毒症患者血浆中HMGB 1水平，其中40例为B。用ELISA法检测37例鼻疽假单胞菌感染和37例其他细菌感染。在兔中制备针对纯化的重组HMGB 1的中和抗体（rab-a-HMGB 1），并在B中评价其作为辅助治疗的潜力。结果：用次优剂量头孢他啶治疗假鼻疽感染的BalB/c小鼠后，B.假鼻疽感染患者的血浆中HMGB 1水平显著高于其他脓毒症患者的血浆（中位数11.1 ng/ml对7.1 ng/ml）。死亡的类鼻疽患者的HMGB 1水平显著高于存活的患者（中位数14.8 ng/ml vs. 9.2 ng/ml）。此外，HMGB 1水平与临床严重程度评分（SOFA评分）显著相关。在小鼠研究中，尽管rab-a-HMGB 1本身不能改善B的存活结果。结论：脓毒症类鼻疽患者血清HMGB 1水平可作为晚期严重脓毒症的标志物。抗HMGB 1中和抗体可作为改善类鼻疽预后的辅助治疗。(C)2014作者由爱思唯尔有限公司代表国际传染病学会出版。
Objectives: A high level of HMGB1 (high-mobility group box 1) -a late onset inflammatory mediator -is a marker of lethal sepsis in several infectious diseases. The level of HMGB1 in the plasma of Burkholderia pseudomallei-infected patients was investigated together with the severity of the disease. The neutralization of HMGB1 to improve survival was also tested in a mouse model.Methods: HMGB1 levels in the plasma of 77 septic patients, 40 with B. pseudomallei infection and 37 with other bacterial infections, were determined by ELISA. Neutralizing antibody against purified recombinant HMGB1 was prepared in rabbits (rab-a-HMGB1) and its potential as an adjunct therapy was evaluated in B. pseudomallei-infected Balb/c mice treated with suboptimal doses of ceftazidime.Results: The plasma from B. pseudomallei-infected patients showed significantly higher HMGB1 levels than the plasma from other septic patients (median 11.1 ng/ml vs. 7.1 ng/ml). The HMGB1 level was significantly higher in patients with melioidosis who died than in those who survived (median 14.8 ng/ml vs. 9.2 ng/ml). Moreover, the HMGB1 level was significantly correlated with the clinical severity score (SOFA score). In the mouse study, although the rab-a-HMGB1 by itself could not improve the survival outcome of B. pseudomallei-infected mice, it could nevertheless enhance the effectiveness of suboptimal doses of ceftazidime in the treatment of these animals.Conclusion: The level of HMGB1 in septic melioidosis patients can be used as a marker of late severe sepsis. Neutralizing antibody to HMGB1 may be used as an adjunct therapy to improve the outcome of melioidosis. (C) 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.