Immune Cell Apoptosis Prevention as Potential Therapy for Severe Infections

摘要

Some labile cell types whose numbers are normallycontrolled through programmed cell death are subject tomarkedly increased destruction during some severe infec-tions. Lymphocytes, in particular, undergo massive andapparently unregulated apoptosis in human patients andlaboratory animals with sepsis, potentially playing a majorrole in the severe immunosuppression that characterizesthe terminal phase of fatal illness. Extensive lymphocyteapoptosis has also occurred in humans and animals infect-ed with several exotic agents, including Bacillus anthracis,the cause of anthrax; Yersinia pestis, the cause of plague;and Ebola virus. Prevention of lymphocyte apoptosis,through either genetic modification of the host or treatmentwith specific inhibitors, markedly improves survival inmurine sepsis models. These findings suggest that inter-ventions aimed at reducing the extent of immune cell apop-tosis could improve outcomes for a variety of severehuman infections, including those caused by emergingpathogens and bioterrorism agents