Prevention of lymphocyte cell death in sepsis improves survival in mice.

摘要: Sepsis induces extensive lymphocyte apoptosis, a process which may be beneficial to host survival by down-regulating the inflammatory response or, alternatively, harmful impairing defenses. To determine vs. adverse effects of apoptosis in sepsis, we blocked either N-benzyloxycarbonyl-Val-Ala-Asp(O-methyl) fluoromethyl ketone (z-VAD), broad-spectrum caspase inhibitor, or use Bcl-2 Ig transgenic mice that selectively overexpress antiapoptotic protein lymphoid pattern. Both z-VAD and prevented resulted marked improvement survival. did not decrease tumor necrosis factor-α production. Considered together, these two studies employing different methods blocking provide compelling evidence immunodepression resulting from loss lymphocytes is central pathogenic event they challenge current paradigm regards sepsis as disorder an uncontrolled response. Caspase inhibitors represent treatment strategy this highly lethal disorder.