Hydrogen sulfide in sepsis: From bench to bedside

Sepsis is a major health problem worldwide. It is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-related deaths represent 19·7% of deaths from all causes worldwide. Outcomes for patients suffering from sepsis are poor, with mortality rates as high as 30-40%, and significant healthcare costs. At present, there is no satisfactory treatment for this condition. Excessive systemic inflammatory response syndrome (SIRS) in acute pancreatitis leads to distant organ damage and multiple organ dysfunction syndrome (MODS), which is the primary cause of morbidity and mortality in this condition. Hydrogen sulfide is produced in the body, and plays an important role in cardiovascular, central nervous and gastrointestinal system. It has also been shown to act as a vasodilator. Using a clinically relevant in vivo model of sepsis, we have shown, for the first time, that endogenously synthesised hydrogen sulfide acts as a mediator of sepsis. We have also made significant strides in our understanding of the mechanism by which hydrogen sulfide contributes to inflammation. Finally, in recent studies, we have shown that hydrogen sulfide can act as an early biomarker for sepsis and bacteraemia. This series of studies have demonstrated the translational potential of our research from the bench to the bedside.