Sepsis is an infection-associated pathological condition that frequently leads to life-threatening and interactive organ failures such as ARDS, circulatory shock, renal failure and DIC. Much basic and clinical research has been conducted to extensively characterize the pathophysiology of sepsis. Although this great research effort has led to accumulated knowledge of the clinical management of sepsis and gradually improved the outcome of patients, sepsis remains the leading cause of death worldwide, with both high mortality and morbidity.
In the previous studies, we found that the plasma levels of histidine-rich protein (HRG) were decreased dramatically and rapidly after the induction of sepsis in mice. A supplementary treatment of mice with purified HRG from human plasma remarkably improved the lethality of mice, whereas the knockdown of HRG production in the liver by siRNA exacerbated the lethality of mice. These findings prompted us to investigate a profile of biological activities of HRG and to clarify the significance of HRG decrease in the cascade of sepsis. Clinical data on plasma levels of HRG in septic patients also suggested the importance of HRG for the understanding of sepsis pathophysiology and estimation of prognosis. We concluded that HRG plays very important roles in maintaining the homeostasis of blood cells, vascular endothelial cells and coagulation.