Neutrophils in the Context of Polymicrobial Sepsis

Sepsis is defined as systemic inflammation in the setting of infection. Sepsis may evolve to severe sepsis and septic shock, which are the end result of complex interactions between infecting organisms and several elements of the host response. The severe forms of sepsis are associated with evidence of organ dysfunction and high lethality rates. This chapter focuses on the putative role of neutrophils in the pathogenesis of sepsis. Neutrophils play essential roles in host defence through their ability to clear bacterial and other infections. To this end, neutrophils have to migrate to the site (focus) of infection where they will phagocytise and kill bacteria and release mediators, necessary for the activation of other cell types. However, failure of neutrophils to migrate into the site of infection may facilitate systemic dissemination of the pathogen leading to release of pathogen, pathogen-associated products and inflammatory mediators in the circulation. The latter, when in high concentrations in the circulation, can activate neutrophils and other leukocytes in the systemic compartment leading to damage of healthy tissues and death. In this chapter, we discuss some of the mechanisms which lead to dysregulated recruitment of neutrophils to the infection focus and their relevance to the development of multi-organ injury and severe sepsis.