Ding Ye, Dai Lu, Xiang Yating, Sun Yue, Yu Juan
Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Institute of Public Health, Nantong University, Nantong 226009, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2020 Sep;36(9):843-848.
Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Immune checkpoint molecules, such as programmed death 1 (PD-1) and PD-1 ligand 1 (PD-L1), are up-regulated during the immunosuppressive phase of sepsis, not only on adaptive immune cells (such as T cells), but also on innate immune cells (such as macrophages, monocytes, neutrophils) as well as non-immune cells, resulting in functional changes, often with adverse sequelae. In numerous pre-clinical models of sepsis, therapeutic agents for blocking engagement of inhibitory immune checkpoints on immune cells have been shown to improve innate and adaptive immune cell functions, increase host resistance to infection and significantly improve survival.
免疫抑制日益被认为是脓毒症期间发病率和死亡率增加的原因之一。先天和适应性免疫系统功能障碍均已被证明会导致根除原发性感染的能力受损，还会导致继发性机会性感染频繁发生。免疫检查点分子，如程序性死亡1（PD-1）和PD-1配体1（PD-L1），在脓毒症的免疫抑制阶段会上调，不仅在适应性免疫细胞（如T细胞）上，也在先天免疫细胞（如巨噬细胞、单核细胞、中性粒细胞）以及非免疫细胞上上调，从而导致功能变化，常常伴有不良后果。在众多脓毒症临床前模型中，已证明用于阻断免疫细胞上抑制性免疫检查点结合的治疗药物可改善先天和适应性免疫细胞功能，增加宿主抗感染能力，并显著提高生存率。
