Apoptosis in sepsis: mechanisms, clinical impact and potential therapeutic targets.
The inability of present therapies to mitigate the devastating effects of sepsis and multiple organ failure in the critically ill patient indicates that more knowledge of the pathophysiology of sepsis is needed if we are to develop better, more effective interventions. This review will examine the concept that a portion of the immune and organ dysfunctions encountered in the septic rodent/ patient is a reflection of not only the types of cells stimulating/ mediating the apoptotic response, but also the varying capacity of the target cell in a given tissue/ organ to perceive these death receptor stimuli as either an apoptotic, inflammatory and/or necrotic signal. We hope the discussion of such studies provides not only new insight into the pathobiology of sepsis, but also suggests possible therapeutic targets for the management of this devastating condition.
Ayala
Alfred
A
Division of Surgical Research, Department of Surgery, Rhode Island Hospital/Brown University School of Medicine, Providence, RI 02903, USA. AAYALA@LIFESPAN.org
Perl
Mario
M
Venet
Fabienne
F
Lomas-Neira
Joanne
J
Swan
Ryan
R
Chung
Chun-Shiang
CS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016638:Critical Illness; D016503:Drug Delivery Systems; D006801:Humans; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D009336:Necrosis / Q000378:metabolism; D012377:Rodentia; D018805:Sepsis / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D015398:Signal Transduction