Apoptosis in sepsis

Abstract

Sepsis demonstrates a marked dysregulation of the immune system in its ability to fight infection. Previous models have focused on the mechanisms which upregulate and sustain the heightened immune response without addressing the role of down-regulation effectors. Attention has been drawn to these down-regulating mechanisms and their precise role in the pathophysiology of sepsis. Apoptosis is an evolutionarily conserved, energy-dependent mode of cell death requiring the initiation and regulation of complex genetic programs. It is the body's main method of getting rid of cells which are in excess, damaged, or no longer needed in a controlled manner. The role of this cellular phenomenon in physiology and pathophysiology has been the subject of intense scrutiny over the last decade. Much work has demonstrated that dysregulation of apoptosis does occur in immune and nonimmune cells in in vitro and in vivo models of sepsis. The difficulty has been in tying the phenomenology of apoptosis into the pathophysiology of sepsis. Further work is needed to make these connections to elucidate rational approaches for clinical applications of immunomodulation in sepsis.