Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock*

Abstract

This is the first prospective study assessing the release over time of HMGB1 in a population of patients with sepsis, severe sepsis, or septic shock. Levels remained high in the majority of patients up to 1 wk after admittance, indicating that the cytokine indeed is a downstream and late mediator of inflammation. Further studies are required to fully define the relationship of HMGB1 to severity of disease.

High mobility group box 1 protein as a marker of hepatocellular injury in human liver transplantation

“…We could not demonstrate any correlation between HMGB1 and TNF-␣ or IL-6 levels. This is in line with previous work on sepsis patients failing to find an association between HMGB1 and various cytokines (IL-6, IL-8, IL-10, and TNF-␣) 12 and reflects the complexity of inflammatory response in the clinical setting. In experimental models, HMGB1 was initially identified as a late acting inflammatory mediator.…”

“…9,10 In clinical sepsis, elevated HMGB1 levels persist for several days, indicating ongoing inflammation. [12][13][14] The rapidly declining HMGB1 levels described in this study argue against prolonged systemic inflammatory response after liver transplantation. Corroborating this, plasma IL-6 declined to presurgery levels quickly after transplantation.…”

“…During liver transplantation, systemic arterial (A) blood samples were collected after induction of anesthesia but before surgery (A0), immediately before initial reperfusion of the graft with portal blood (A1), 10 minutes after portal vein declamping (A2), 10 minutes after hepatic artery declamping (A3), and 8, 24, and 48 hours after reperfusion. To assess changes across the graft, blood sam- 12,20 Normal plasma samples containing known amounts of recombinant HMGB1 were analyzed equally in each gel, and a standard curve was generated to calculate sample HMGB1 levels.…”

“…9,10 After local tissue injury, HMGB1 initiates systemic inflammation and injury at the end organ level. 11 In the clinical setting, elevated serum HMGB1 levels have been described in sepsis, 9,12,13 pneumonia, 14 and acute pancreatitis 15 and following cerebral and myocardial ischemia. 16 Recently, HMGB1 was described as an early inflammatory mediator after acute local organ injury.…”

Is the septic response good or bad?

“…High-mobility group box 1 protein HMGB-1 functions as a late-acting proinflammatory mediator of sepsis, and it circulates in high concentrations in the majority of septic patients [43,44]. It is secreted by activated immune cells and elicits prolonged activation of cells, either directly or more likely indirectly via substances bound to HMGB1, via the receptor for advanced glycation end products, TLR2, and TLR4 [45].…”