Alireza R. Rezaie, Jung-Sup Bae
The high mobility group box 1 protein (HMGB1) has been identified as a potent pro-inflammatory extracellular cytokine and a late mediator of endotoxin lethality in mice. It can be secreted into intravascular spaces by cells of the innate immune system or passively released by damaged tissues and necrotic cells in response to bacterial endotoxin and/or trauma. It has also been demonstrated that HMGB1 can be released from human endothelial cells in response to both endotoxin and TNF-α.
Activation of the endothelium by pro-inflammatory cytokines during infection plays an important pathophysiological role in the chain of events that may lead to the septic shock/severe sepsis syndrome. The results presented above, together with those previously reported by others, suggest that vascular endothelial cells may be rich sources of HMGB1 which can be released in response to bacterial endotoxin and endogenously expressed pro-inflammatory cytokines, thereby contributing to the pathology of severe sepsis. In support of HMGB1 playing an important pathological role in severe sepsis, it has been found that high plasma levels of HMGB1 in patients with severe sepsis and in animal models of endotoxemia correlate with higher mortality.
The present invention provides methods for treating sepsis comprising administering to an individual an effective amount of PCgla/MeizoTh.