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Published on: February 24, 2023
High HMGB1 level is associated with poor outcome of septicemic melioidosis
Jaruek Charoensup1, Rasana W Sermswan2, Arunee Paeyao1
1Melioidosis Research Center, Khon Kaen University, Khon Kaen, Thailand.
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.
Insights
High-mobility group box 1 (HMGB1) levels indicate lethal sepsis in melioidosis patients. Neutralizing HMGB1 may improve outcomes when used with antibiotics in severe sepsis cases.
Area of Science:
- Infectious Diseases
- Immunology
- Critical Care Medicine
Background:
- High-mobility group box 1 (HMGB1) is a late inflammatory mediator associated with lethal sepsis.
- Elevated HMGB1 levels are observed in various infectious diseases.
Purpose of the Study:
- To investigate HMGB1 plasma levels in Burkholderia pseudomallei-infected patients.
- To assess the correlation between HMGB1 levels and disease severity.
- To evaluate HMGB1 neutralization as an adjunct therapy in a mouse model.
Main Methods:
- HMGB1 plasma levels were measured using ELISA in 77 septic patients (40 with B. pseudomallei, 37 with other infections).
- A neutralizing antibody against HMGB1 was developed in rabbits.
- The efficacy of the antibody as an adjunct therapy with ceftazidime was tested in B. pseudomallei-infected mice.
Main Results:
- B. pseudomallei patients had significantly higher HMGB1 levels than other septic patients (median 11.1 vs. 7.1 ng/ml).
- HMGB1 levels were higher in non-surviving melioidosis patients (median 14.8 vs. 9.2 ng/ml) and correlated with SOFA scores.
- HMGB1 antibody enhanced suboptimal ceftazidime treatment effectiveness in mice but did not improve survival alone.
Conclusions:
- HMGB1 plasma levels serve as a marker for late, severe sepsis in melioidosis.
- HMGB1 neutralization shows potential as an adjunctive therapy to improve melioidosis outcomes.
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