Circulating high-mobility group box 1 (HMGB1) concentrations are elevated in both uncomplicated pneumonia and pneumonia with severe sepsis*

Abstract

HMGB1 is elevated in almost all CAP subjects, and higher circulating HMGB1 is associated with mortality. But immunodetectable HMGB1 levels were also persistently elevated in those patients who fared well. Thus, additional work is needed to understand the biological activities of serum HMGB1 in sepsis.

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

“…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.…”

“…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.…”

HMGB1 Develops Enhanced Proinflammatory Activity by Binding to Cytokines

“…As shown in the present experiments, relatively short periods of interaction between HMGB1 and extracellular proteins are sufficient to result in binding. The concentrations of HMGB1 used in our studies (100 ng/ml) are often exceeded for prolonged periods in plasma during severe infection (15,37). It is therefore possible that HMGB1 binds to cytokines and other proinflammatory mediators, including LPS, during the early stages of sepsis, pneumonia, and conditions associated with severe infection or organ dysfunction.…”

“…In acute inflammatory states, such as sepsis, plasma concentrations of HMGB1 are elevated for prolonged periods of days to weeks, and they are present even as the patient's condition is improving (15,37). Tissue concentrations of HMGB1 secreted by activated cells and released during apoptosis and necrosis are likely to be even higher in such acute inflammatory states.…”

“…Circulating levels of HMGB1 remain elevated in patients recovering from severe pneumonia, even though there is improvement in organ system dysfunction and overall clinical status, indicating that HMGB1 does not produce continuing inflammatory injury in this setting (15). In two studies using rigorous purification techniques, highly purified HMGB1 did not appear to be capable of inducing cellular activation unless bound to DNA-containing immune complexes or to incompletely characterized bacterial products (16,17).…”