Anti-cytokine therapies in response to systemic infection
Anti-cytokine therapies in response to systemic infection
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DOI：
10.1046/j.0022-202x.2001.00046.x
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发表时间：
2001-12-01
影响因子：
--
通讯作者：
Dinarello, CA
中科院分区：
文献类型：
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作者：
Dinarello, CA
在过去的5年中，脓毒症综合征患者的28d死亡率有所下降，但仍在30%~40%之间，感染性休克和多器官衰竭患者的死亡率较高。尽管重症监护病房提供血流动力学、代谢、呼吸和肾脏支持，但仍观察到如此高的死亡率。显然，一些患者在磨难中幸存下来，但仍令人沮丧的是，无法阻止导致这些患者多器官衰竭和死亡的下坡路。已经寻找和测试了新的治疗方法，包括那些阻止两种促炎细胞因子-白介素1(IL-1)和肿瘤坏死因子(TNF)的生物活性的方法。在动物研究的基础上，抗肿瘤坏死因子和白介素1疗法被用来“拯救”面对相当大的支持努力而继续恶化的病人。不幸的是，在涉及近10000名患者的双盲安慰剂对照试验中，这些抗细胞因子治疗并没有显著降低28天的死亡率，尽管与抗细胞因子治疗相关的死亡率有持续但在统计学上没有显著的下降。另一方面，同样的基于肿瘤坏死因子和白介素1的治疗方法在类风湿性关节炎的局部炎症和进展方面取得了显著的改善。似乎脓毒症的全身性炎症需要的不仅仅是抗细胞因子的单一治疗，才能显著降低死亡率。
In the past 5 y, the 28 d mortality in patients with sepsis syndrome has decreased somewhat but still ranges from 30% to 40%; mortality in those patients with septic shock and multiple organ failure is higher. This high mortality is observed despite intensive care units that deliver hemodynamic, metabolic, ventilatory, and renal support. Clearly some patients survive the ordeal but it remains frustrating not being able to stop the downhill course leading to multiple organ failure and death in these patients. New therapies have been sought and tested, including those preventing the biologic activity of two pro-inflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF). Based on animal studies, anti-TNF and IL-1 therapy has been used to "rescue" the patient who continues to deteriorate in the face of considerable support efforts. Unfortunately, these anticytokine therapies have not dramatically reduced 28 d mortality in double-blind, placebo-controlled trials involving nearly 10 000 patients, although there is a consistent but statistically nonsignificant decrease in mortality associated with anticytokine therapies. On the other hand, the same and-TNF and IL-1-based therapies have made a dramatic improvement in the local inflammation and progression of rheumatoid arthritis. It appears that systemic inflammation of sepsis requires more than anticytokine monotherapy to significantly reduce mortality.