Lee Song I, Kim Na Young, Chung Chaeuk, Park Dongil, Kang Da Hyun, Kim Duk Ki, Yeo Min-Kyung, Sun Pureum, Lee Jeong Eun
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Chungnam National University Hospital, 282 Munhwa-Ro, Jung-Gu, Daejeon, 35015, Republic of Korea.
Cancer Research Institute, Chungnam National University, Munhwa-Ro 266, Daejeon, 35015, Republic of Korea.
BMC Immunol. 2025 Jan 14;26(1):3. doi: 10.1186/s12865-024-00679-z.
Interleukin-6 (IL-6) plays a central role in sepsis-induced cytokine storm involving immune hyperactivation and early neutrophil activation. Programmed death protein-1 (PD-1) is associated with sepsis-induced immunosuppression and lymphocyte apoptosis. However, the effects of simultaneous blockade of IL-6 and PD-1 in a murine sepsis model are not well understood.
In this study, sepsis was induced in male C57BL/6 mice through cecal ligation and puncture (CLP). IL-6 blockade, PD-1 blockade, or combination of both was administered 24 h after CLP. Peripheral blood count, cytokine level, lymphocyte apoptosis in the spleen, neutrophil infiltration in the lungs and liver, and survival rate were measured. The mortality rate of the IL-6/PD-1 group was lower, though not statistically significant (p = 0.164), than that of CLP mice (75.0% vs. 91.7%). The IL-6/PD-1 group had lower neutrophil percentage and platelet count compared with the CLP group; no significant difference was observed in other cytokine levels. The IL-6/PD-1 group also showed reduced T lymphocyte apoptosis in the spleen and decreased neutrophil infiltration in the liver and lungs.
IL-6/PD-1 dual blockade reduces neutrophil infiltration, lymphocyte apoptosis, and bacterial burden while preserving tissue integrity in sepsis. Although the improvement in survival was not statistically significant, these findings highlight its potential as a therapeutic approach in sepsis.
白细胞介素-6（IL-6）在脓毒症诱导的细胞因子风暴中起核心作用，涉及免疫过度激活和早期中性粒细胞活化。程序性死亡蛋白-1（PD-1）与脓毒症诱导的免疫抑制和淋巴细胞凋亡有关。然而，在小鼠脓毒症模型中同时阻断IL-6和PD-1的效果尚不清楚。
在本研究中，通过盲肠结扎和穿刺（CLP）诱导雄性C57BL/6小鼠发生脓毒症。在CLP后24小时给予IL-6阻断、PD-1阻断或两者联合治疗。测量外周血细胞计数、细胞因子水平、脾脏中的淋巴细胞凋亡、肺和肝脏中的中性粒细胞浸润以及存活率。IL-6/PD-1组的死亡率低于CLP小鼠（75.0%对91.7%），尽管差异无统计学意义（p = 0.164）。与CLP组相比，IL-6/PD-1组的中性粒细胞百分比和血小板计数较低；在其他细胞因子水平上未观察到显著差异。IL-6/PD-1组还显示脾脏中T淋巴细胞凋亡减少，肝脏和肺中的中性粒细胞浸润减少。
IL-6/PD-1双重阻断可减少中性粒细胞浸润、淋巴细胞凋亡和细菌负荷，同时在脓毒症中保持组织完整性。尽管生存率的改善无统计学意义，但这些发现突出了其作为脓毒症治疗方法的潜力。
