Department of Anesthesiology, Shanghai Dermatology Hospital, Shanghai, China (mainland).
Department of Anesthesiology, Tenth People's Hospital, Tongji University, Shanghai, China (mainland).
Med Sci Monit. 2018 Jul 11;24:4798-4806. doi: 10.12659/MSM.908242.
BACKGROUND Sepsis causes the highest mortality in non-cardiovascular intensive care units worldwide. Recent research has demonstrated that the late phase of sepsis, characterized as septic immunosuppression, is the central pathophysiological mechanism of immune dysfunction. Investigating the suppressive mechanism of immune cells may identify possible targets for therapy. MATERIAL AND METHODS We used LPS 2-hit model for dendritic cells (DCs) to establish endotoxin tolerance, and co-cultured with splenocytes. Co-culture responses and gene expressions were evaluated. RESULTS Endotoxin tolerant DCs showed irresponsiveness in pro-inflammatory cytokine production and expressed negative regulator genes of inflammation. When co-cultured with splenocytes, suppression of inflammatory responses and T cells apoptosis were observed with elevated expression of IRAK-M and PDL-1, and interference and neutralization of these 2 molecules led to partly reversed suppression of inflammation. CONCLUSIONS Our research found direct regulation of endotoxin tolerant DCs to other immune cells and suggested a possible mechanism via IRAK-M and PDL-1. This may inform research on septic immunosuppression and suggests possible therapeutic targets for sepsis.
脓毒症是全球非心血管重症监护病房中死亡率最高的疾病。最近的研究表明，脓毒症的晚期阶段，即脓毒症免疫抑制，是免疫功能障碍的中心病理生理机制。研究免疫细胞的抑制机制可能有助于确定潜在的治疗靶点。
我们使用 LPS 2 次打击模型建立树突状细胞（DCs）的内毒素耐受，并与脾细胞共培养。评估共培养反应和基因表达。
内毒素耐受的 DCs 在产生促炎细胞因子方面表现出无反应性，并表达炎症的负调节基因。与脾细胞共培养时，观察到炎症反应和 T 细胞凋亡的抑制，同时 IRAK-M 和 PDL-1 的表达升高，干扰和中和这 2 种分子可部分逆转炎症抑制。
我们的研究发现内毒素耐受的 DCs 对其他免疫细胞的直接调节，并提出了一种可能通过 IRAK-M 和 PDL-1 的机制。这可能为脓毒症免疫抑制的研究提供信息，并为脓毒症提供可能的治疗靶点。
