High HMGB1 level is associated with poor outcome of septicemic melioidosis

Abstract

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. 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. 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. 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.