Remy Solenn, Kolev-Descamps Karine, Gossez Morgane, Venet Fabienne, Demaret Julie, Javouhey Etienne, Monneret Guillaume
Hospices Civils de Lyon, Paediatric Intensive Care Unit, Mother and Children University Hospital, 59 Boulevard Pinel, 69500, Bron, France.
Hospices Civils de Lyon, Immunology Laboratory, E. Herriot Hospital, 69003, Lyon, France.
Ann Intensive Care. 2018 Mar 13;8(1):36. doi: 10.1186/s13613-018-0382-x.
While the process of sepsis-induced immunosuppression is now well described in adults, very little information is available on immune functions in pediatric sepsis. The current study investigated this in children with septic shock by performing immunomonitoring, including both innate (monocyte human leukocyte antigen-DR, mHLA-DR, expression) and adaptive immunity (lymphocyte subsets count), as well as cytokine concentrations (IL-6, IL-8, IL-10, IL-1Ra, TNF-α, IFN-γ). Subsequent objectives were to assess the associations between inflammatory response, potential immunosuppression and secondary acquired infection occurrence.
Single-center prospective observational study, including children aged between 1 month and 18 years admitted to pediatric intensive care unit (PICU) for septic shock. Age-matched controls were children hospitalized for elective surgery without any infectious criteria. Blood was sampled at day 1-2, 3-5, and 7-9 after sepsis onset. mHLA-DR and lymphocyte subsets count were measured by flow cytometry and cytokine concentrations by Luminex technology.
A total of 26 children and 30 controls were included. Patients had lymphopenia, and mHLA-DR levels were significantly lower than controls at each time point (p < 0.0001). All cytokines peaked at day 1-2. Children with secondary acquired infection had lower day 3-5 mHLA-DR and higher pro-inflammatory cytokine concentrations (IL-6, IL-8 and TNF-α) at day 1-2 compared to children without secondary acquired infection.
The higher initial inflammatory cytokine production was, the more innate immunity was altered, while evaluated by low mHLA-DR expression. Children with decreased mHLA-DR expression developed more secondary acquired infections. Upon confirmation in multicenter cohorts, these results pave the way for immunostimulation for the most immunosuppressed children in order to prevent nosocomial infections in PICU. Trial registration PedIRIS study NCT02848144. Retrospectively registered 28 July 2016.
虽然脓毒症诱导的免疫抑制过程在成人中已有详细描述，但关于儿童脓毒症免疫功能的信息却非常有限。本研究通过进行免疫监测，包括先天免疫（单核细胞人类白细胞抗原-DR，mHLA-DR，表达）和适应性免疫（淋巴细胞亚群计数）以及细胞因子浓度（IL-6、IL-8、IL-10、IL-1Ra、TNF-α、IFN-γ），对脓毒性休克患儿进行了调查。后续目标是评估炎症反应、潜在免疫抑制与继发性获得性感染发生之间的关联。
单中心前瞻性观察性研究，纳入因脓毒性休克入住儿科重症监护病房（PICU）年龄在1个月至18岁之间的儿童。年龄匹配的对照组为因择期手术住院且无任何感染标准的儿童。在脓毒症发作后第1 - 2天、3 - 5天和7 - 9天采集血液。通过流式细胞术测量mHLA-DR和淋巴细胞亚群计数，通过Luminex技术测量细胞因子浓度。
共纳入26例患儿和30例对照。患者出现淋巴细胞减少，在每个时间点mHLA-DR水平均显著低于对照组（p < 0.0001）。所有细胞因子在第1 - 2天达到峰值。与无继发性获得性感染的儿童相比，继发性获得性感染的儿童在第3 - 5天mHLA-DR较低，在第1 - 2天促炎细胞因子浓度（IL-6、IL-8和TNF-α）较高。
通过低mHLA-DR表达评估，初始炎症细胞因子产生越高，先天免疫改变越明显。mHLA-DR表达降低的儿童发生更多继发性获得性感染。在多中心队列中得到证实后，这些结果为对免疫抑制最严重的儿童进行免疫刺激以预防PICU医院感染铺平了道路。试验注册：PedIRIS研究NCT02848144。2016年7月28日追溯注册。
