Hotchkiss Richard S, Nicholson Donald W
Department of Anesthesiology, Washington University School of Medicine, Campus Box 8054, 660 South Euclid, St Louis, Missouri 63110, USA.
Nat Rev Immunol. 2006 Nov;6(11):813-22. doi: 10.1038/nri1943. Epub 2006 Oct 13.
Although the prevailing concept has been that mortality in sepsis results from an unbridled hyper-inflammatory cytokine-mediated response, the failure of more than 30 clinical trials to treat sepsis by controlling this cytokine response requires a 'rethink' of the molecular mechanism underpinning the development of sepsis. As we discuss here, remarkable new studies indicate that most deaths from sepsis are actually the result of a substantially impaired immune response that is due to extensive death of immune effector cells. Rectification of this apoptotic-inflammatory imbalance using modulators of caspases and other components of the cell-death pathway have shown striking efficacy in stringent animal models of sepsis, indicating an entirely novel path forward for the clinical treatment of human sepsis.
尽管普遍的观念认为脓毒症中的死亡是由不受控制的高炎症细胞因子介导的反应所致，但超过30项通过控制这种细胞因子反应来治疗脓毒症的临床试验均告失败，这就需要对脓毒症发生发展的分子机制进行“重新思考”。正如我们在此所讨论的，引人注目的新研究表明，脓毒症导致的大多数死亡实际上是免疫反应严重受损的结果，而这种受损是由于免疫效应细胞大量死亡所致。在严格的脓毒症动物模型中，使用半胱天冬酶调节剂和细胞死亡途径的其他成分来纠正这种凋亡-炎症失衡已显示出显著疗效，这为人类脓毒症的临床治疗指明了一条全新的道路。
