Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach

被引:1106
作者
Hotchkiss, Richard S. [1 ]
Monneret, Guillaume [2 ]
Payen, Didier [3 ,4 ]
机构
[1] Washington Univ, Sch Med, Dept Anesthesiol Med & Surg, St Louis, MO 63110 USA
[2] Hosp Civils Lyon, Hop E, Immunol Lab, Lyon, France
[3] Hop Lariboisiere, AP HP, Dept Anaesthesiol & Crit Care, F-75475 Paris, France
[4] Hop Lariboisiere, AP HP, SAMU, F-75475 Paris, France
基金
美国国家卫生研究院;
关键词
INTENSIVE-CARE PATIENTS; IMPROVES SURVIVAL; INTERFERON-GAMMA; SEPTIC SHOCK; IMMUNE DYSFUNCTION; PD-1; EXPRESSION; DOWN-REGULATION; WHOLE-BLOOD; T-CELLS; MORTALITY;
D O I
10.1016/S1473-3099(13)70001-X
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Failures of highly touted trials have caused experts to call for re-evaluation of the current approach toward sepsis. New research has revealed key pathogenic mechanisms; autopsy results have shown that most patients admitted to intensive care units for treatment of sepsis had unresolved septic foci at post mortem, suggesting that patients were unable to eradicate invading pathogens and were more susceptible to nosocomial organisms, or both. These results suggest that therapies that improve host immunity might increase survival. Additional work showed that cytokine production by splenocytes taken post mortem from patients who died of sepsis is profoundly suppressed, possibly because of so-called T-cell exhaustion a newly recognised immunosuppressive mechanism that occurs with chronic antigenic stimulation. Results from two clinical trials of biomarker-guided therapeutic drugs that boosted immunity showed promising findings in sepsis. Collectively, these studies emphasise the degree of immunosuppression that occurs in sepsis, and explain why many previous sepsis trials which were directed at blocking inflammatory mediators or pathogen recognition signalling pathways failed. Finally, highly encouraging results from use of the new immunomodulatory molecules interleukin 7 and anti-programmed cell death 1 in infectious disease point the way for possible use in sepsis. We hypothesise that immunoadjuvant therapy represents the next major advance in sepsis.
引用
收藏
页码:260 / 268
页数:9
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