Zorio Violette, Venet Fabienne, Delwarde Benjamin, Floccard Bernard, Marcotte Guillaume, Textoris Julien, Monneret Guillaume, Rimmelé Thomas
Department of Anesthesiology and Critical Care Medicine, Edouard Herriot hospital, Hospices Civils de Lyon, Lyon, France.
EA7426 Hospices Civils de Lyon - bioMérieux, University Claude Bernard Lyon 1 "Pathophysiology of Injury Induced Immunosuppression", Lyon, France.
Ann Intensive Care. 2017 Dec;7(1):80. doi: 10.1186/s13613-017-0304-3. Epub 2017 Aug 2.
Increase in mortality and in recurrent infections in the year following ICU discharge continues in survivors of septic shock, even after total clinical recovery from the initial septic event and its complications. This supports the hypothesis that sepsis could induce persistent long-term immune dysfunctions. To date, there is almost no data on ICU discharge and long-term evolution of sepsis-induced immunosuppression in septic shock survivors. The aim of this study was to assess the persistence of sepsis-induced immunosuppression by measuring expression of human leukocyte antigen DR on monocytes (mHLA-DR), CD4+ T cells, and regulatory T cells (Treg) at ICU discharge and 6 months after ICU discharge in patients admitted to the ICU for septic shock.
In this prospective observational study, septic shock survivors with no preexisting immune suppression or treatment interfering with the immune system were included. mHLA-DR, CD4+ T cells, and Treg expression were assessed on day 1-2, 3-4, and 6-8 after ICU admission, at ICU discharge, and 6 months after ICU discharge.
A total of 40 patients were enrolled during their ICU stay: 21 males (52.5%) and 19 females, median age 68 years (IQR 58-77), median SOFA score on day 1-2 was 8 (IQR 7-9), and median ICU length of stay was 11 days (IQR 7-24). Among these 40 patients, 33 were studied at ICU discharge and 15 were disposed for blood sampling 6 months after ICU discharge. On day 1-2, mHLA-DR expression was abnormally low for all patients [median 4212 (IQR 2640-6047) AB/C] and remained abnormally low at ICU discharge for 75% of them [median 10,281 (IQR 7719-13,035) AB/C]. On day 3-4, 46% of patients presented CD4+ lymphopenia [median 515 (IQR 343-724) mm] versus 34% at ICU discharge [median 642 (IQR 459-846) mm]. Among patients with a 6-month blood sample, normal values of mHLA-DR were found for all patients [median 32,616 (IQR 24,918-38,738) AB/C] except for one and only another one presented CD4+ lymphopenia.
While immune alterations persist at ICU discharge, there is, at cellular level, no persistent immune alterations among septic shock survivors analyzed 6 months after ICU discharge.
脓毒性休克幸存者在重症监护病房（ICU）出院后的一年内死亡率和反复感染率持续上升，即便最初的脓毒症事件及其并发症已完全临床康复。这支持了脓毒症可诱发持续性长期免疫功能障碍的假说。迄今为止，几乎没有关于脓毒性休克幸存者ICU出院情况及脓毒症诱导的免疫抑制长期演变的数据。本研究的目的是通过测量入住ICU治疗脓毒性休克患者在ICU出院时及出院后6个月时单核细胞（mHLA-DR）、CD4 + T细胞和调节性T细胞（Treg）上人类白细胞抗原DR的表达，来评估脓毒症诱导的免疫抑制的持续性。
在这项前瞻性观察研究中，纳入了既往无免疫抑制或无干扰免疫系统治疗的脓毒性休克幸存者。在ICU入院后第1 - 2天、3 - 4天、6 - 8天、ICU出院时及出院后6个月评估mHLA-DR、CD4 + T细胞和Treg的表达。
共有40例患者在ICU住院期间入组：男性21例（52.5%），女性19例，中位年龄68岁（四分位间距58 - 77岁），第1 - 2天的中位序贯器官衰竭评估（SOFA）评分是8分（四分位间距7 - 9分），中位ICU住院时间为11天（四分位间距7 - 24天）。在这40例患者中，33例在ICU出院时接受了研究，15例在ICU出院后6个月进行了血样采集。在第1 - 2天，所有患者的mHLA-DR表达均异常低[中位值4212（四分位间距2640 - 6047）AB/C]，其中75%的患者在ICU出院时仍异常低[中位值10281（四分位间距7719 - 13035）AB/C]。在第3 - 4天，46%的患者出现CD4 +淋巴细胞减少[中位值515（四分位间距343 - 724）/mm]，而在ICU出院时这一比例为34%[中位值642（四分位间距459 - 846）/mm]。在有6个月血样的患者中，除1例患者外，所有患者的mHLA-DR值均正常[中位值32616（四分位间距24918 - 38738）AB/C]，只有另1例出现CD4 +淋巴细胞减少。
虽然在ICU出院时免疫改变仍然存在，但在细胞水平上，对ICU出院后6个月分析的脓毒性休克幸存者而言，不存在持续性免疫改变。
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