PMN and Lymphocyte Apoptosis in the Critically Ill: Different Means, Similar Outcome

Accidental traumatic injury remains the fifth leading cause of death in America Behind heart disease, cancer, stroke and lung disease. Frequently, patients that survive the initial injury and do not succumb to major central nervous system or internal organ damage during the first day develop inflammatory complications, which result in morbidity and mortality due to multiple organ failure/dysfunction. These complications include non-septic inflammation of damaged tissue/organs, the adult respiratory distress syndrome (ARDS), and sepsis. While apoptosis, or programmed cell death, was initially understood as a mechanism by which cells of the immune system are cleared as a means of natural cell turnover or resolution of an inflammatory response, dysregulated apoptosis can be detrimental to the organism. Here we will briefly summarize data from both experimental animal models and critically ill patients that address (1) the suppression of neutrophil apoptosis in the critically ill, (2) the increase of lymphocyte (B and T cell) apoptosis, which leads to immunosuppression, (3) inflammatory mediators, such as cytokines, which appear to play predominant roles in neutrophil and lymphocyte apoptosis, and (4) the importance of the Bcl-2 familty in the regulation of apoptosis in the critically ill. These data clearly demonstrate the complexity of the apoptotic response and, thus, justify the need to increase our understanding of apoptosis in the critically ill. Such information will provide us with new insights, and possibly offer better therapeutic targets for the management of these devastating conditions.