de Roquetaillade Charles, Monneret Guillaume, Gossez Morgane, Venet Fabienne
EA7426 "Pathophysiology of Injury-Induced Immunosuppression (PI3)", Université Claude Bernard Lyon 1, Lyon, France.
EA7426 "Pathophysiology of Injury-Induced Immunosuppression (PI3)", Université Claude Bernard Lyon 1, Lyon, France; Immunology Laboratory, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France.
Crit Rev Immunol. 2018;38(6):433-451. doi: 10.1615/CritRevImmunol.2018027460.
Sepsis, defined as life-threatening organ dysfunction caused by dysregulated host response to infection, has recently been acknowledged as a worldwide health priority. Sepsis remains the leading cause of mortality in intensive care units and accounts for 6 million deaths every year. Few therapeutic options targeting host immune response in sepsis have demonstrated their efficacy so far. Increasing evidence suggests that a profound immune suppression develops following sepsis, affecting innate and adaptive immune response, of which intensity and duration is associated with increased risk of death and nosocomial infection. Immunostimulant treatments are thus now evaluated in sepsis, and recombinant human IL-7 (rhIL-7) represents a promising candidate. rhIL-7 has been evaluated in several clinical trials in patients with altered lymphocytic responses (HIV infection, hematopoietic stem cell transplantation, and cancer). Recent studies in animal models and in patients' samples ex vivo demonstrated its efficacy in improving sepsis-induced T cell alterations. Finally, the first clinical trial evaluating rhIL-7 in septic shock patients has just been published. This review will discuss the use of rhIL-7 to treat sepsis-induced T cell dysfunction by introducing the pathophysiology of sepsis and sepsis-related lymphocyte alterations before focusing on rhIL-7 and its potential use of as a therapeutic intervention in patients.
脓毒症被定义为由宿主对感染的反应失调引起的危及生命的器官功能障碍,最近已被公认为全球卫生重点问题。脓毒症仍然是重症监护病房死亡的主要原因,每年导致600万人死亡。迄今为止,针对脓毒症宿主免疫反应的治疗选择很少显示出疗效。越来越多的证据表明,脓毒症后会出现严重的免疫抑制,影响先天性和适应性免疫反应,其强度和持续时间与死亡风险和医院感染风险增加相关。因此,目前正在脓毒症中评估免疫刺激治疗,重组人白细胞介素-7(rhIL-7)是一个有前景的候选药物。rhIL-7已在淋巴细胞反应改变的患者(HIV感染、造血干细胞移植和癌症)中进行了多项临床试验评估。最近在动物模型和患者离体样本中的研究证明了其在改善脓毒症诱导的T细胞改变方面的疗效。最后,评估rhIL-7在感染性休克患者中的第一项临床试验刚刚发表。本综述将通过介绍脓毒症的病理生理学和脓毒症相关的淋巴细胞改变,来讨论rhIL-7在治疗脓毒症诱导的T细胞功能障碍中的应用,然后重点关注rhIL-7及其作为患者治疗干预措施的潜在用途。