[Role of histamine in sepsis-induced organ dysfunction: study using knockout mice of histamine-related genes]

Sepsis is the leading cause of death in critically ill patients, and its incidence continues to rise. Sepsis is now defined as life-threatening organ dysfunction due to a dysregulated host response to infection. Histamine assumes a critical role as a major mediator of many pathologic disorders with inflammation and immune reactions. However, direct evidence has not been provided showing the involvement of histamine in the development of multiple organ dysfunction or failure in sepsis. We have found that sepsis-induced major end-organ (lung, liver, and kidney) injury is attenuated in histidine decarboxylase (HDC) gene knockout mice. H1/H2-receptor gene-double knockout mice apparently behave similar to HDC knockout mice in reducing sepsis-related pathologic changes. Here we provide an overview on the role of endogenous histamine as an aggregating mediator that could contribute to the development of major end-organ injury in sepsis.