Pro-resolution of Inflammation: New Hints to Manage Sepsis?

Abstract

Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The pathophysiological mechanism of sepsis is highly complex, and the mortality of in-patients suffering from sepsis is more than 10%. Severe unmanaged inflammation and inappropriate immune response characterize sepsis. Anti-inflammation therapies alone are not successful for the reason that disbalance of anti-inflammatory and pro-resolving agents. In the recent researches, the host responses during the course of self-resolving infections are found to have the involvements of specialized pro-resolution mediators (SPMs), namely, lipoxins, resolvins, protectins and maresins. These endogenous lipid metabolites are core signal molecules in the resolution of inflammation, playing a key role in regulating the inflammation and promoting return to homeostasis. Besides, heme oxygenase-1 (HO-1, a sensitive marker for oxidative stress) is also known for upregulation in inflammation profiling. Carbon monoxide, synthesized by HO-1, performs multiple stances of anti-inflammation and pro-resolution along with the SPMs. If the potentially beneficial effects of these mediators would be well evaluated in clinical trials, they present encouraging new hints in managing infectious maladies especially sepsis.