High HMGB1 level is associated with poor outcome of septicemic melioidosis

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...

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Main Authors: Jaruek Charoensup, Rasana W. Sermswan, Arunee Paeyao, Sairavee Promakhejohn, Sirilak Punasee, Charanya Chularari, Sukunya Krabkraikaew, Sujet Lertanekawattana, Surasakdi Wongratanacheewin
Format: Article
Language:English
Published: Elsevier 2014-11-01
Series:International Journal of Infectious Diseases
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Online Access:http://www.sciencedirect.com/science/article/pii/S1201971214016105
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author Jaruek Charoensup
Rasana W. Sermswan
Arunee Paeyao
Sairavee Promakhejohn
Sirilak Punasee
Charanya Chularari
Sukunya Krabkraikaew
Sujet Lertanekawattana
Surasakdi Wongratanacheewin
author_facet Jaruek Charoensup
Rasana W. Sermswan
Arunee Paeyao
Sairavee Promakhejohn
Sirilak Punasee
Charanya Chularari
Sukunya Krabkraikaew
Sujet Lertanekawattana
Surasakdi Wongratanacheewin
author_sort Jaruek Charoensup
collection DOAJ
description 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.
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spelling doaj.art-46968da0269e49ac8f2ca42e1f5223cb2022-12-22T02:49:13ZengElsevierInternational Journal of Infectious Diseases1201-97121878-35112014-11-0128C11111610.1016/j.ijid.2014.07.025High HMGB1 level is associated with poor outcome of septicemic melioidosisJaruek Charoensup0Rasana W. Sermswan1Arunee Paeyao2Sairavee Promakhejohn3Sirilak Punasee4Charanya Chularari5Sukunya Krabkraikaew6Sujet Lertanekawattana7Surasakdi Wongratanacheewin8Melioidosis Research Center, Khon Kaen University, Khon Kaen, ThailandMelioidosis Research Center, Khon Kaen University, Khon Kaen, ThailandMelioidosis Research Center, Khon Kaen University, Khon Kaen, ThailandNong Khai Hospital, Nong Khai, ThailandMahasarakham Hospital, Mahasarakham, ThailandMahasarakham Hospital, Mahasarakham, ThailandNong Khai Hospital, Nong Khai, ThailandNong Khai Hospital, Nong Khai, ThailandMelioidosis Research Center, Khon Kaen University, Khon Kaen, ThailandObjectives: 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.http://www.sciencedirect.com/science/article/pii/S1201971214016105Burkholderia pseudomalleiMelioidosisHMGB1Sepsis
spellingShingle Jaruek Charoensup
Rasana W. Sermswan
Arunee Paeyao
Sairavee Promakhejohn
Sirilak Punasee
Charanya Chularari
Sukunya Krabkraikaew
Sujet Lertanekawattana
Surasakdi Wongratanacheewin
High HMGB1 level is associated with poor outcome of septicemic melioidosis
International Journal of Infectious Diseases
Burkholderia pseudomallei
Melioidosis
HMGB1
Sepsis
title High HMGB1 level is associated with poor outcome of septicemic melioidosis
title_full High HMGB1 level is associated with poor outcome of septicemic melioidosis
title_fullStr High HMGB1 level is associated with poor outcome of septicemic melioidosis
title_full_unstemmed High HMGB1 level is associated with poor outcome of septicemic melioidosis
title_short High HMGB1 level is associated with poor outcome of septicemic melioidosis
title_sort high hmgb1 level is associated with poor outcome of septicemic melioidosis
topic Burkholderia pseudomallei
Melioidosis
HMGB1
Sepsis
url http://www.sciencedirect.com/science/article/pii/S1201971214016105
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