Ebihara Takeshi, Matsumoto Hisatake, Matsubara Tsunehiro, Matsuura Hiroshi, Hirose Tomoya, Shimizu Kentaro, Ogura Hiroshi, Kang Sujin, Tanaka Toshio, Shimazu Takeshi
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Immune Regulation, Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Shock. 2021 Nov 1;56(5):718-726. doi: 10.1097/SHK.0000000000001756.
Cytokines compose a network and play crucial roles in the pathogenesis and prognosis of sepsis. Adipose tissue is an important immune endocrine organ that releases adipocytokines. This study aimed to evaluate adipocytokines in sepsis from a network perspective.
This retrospective study of 37 patients with sepsis and 12 healthy controls was conducted from February 2014 to July 2015. Blood samples were collected from patients on days 1 (within 24 h of diagnosis), 2, 4, 6, 8, 11, and 15 and from healthy controls. Adipocytokines (adiponectin, leptin, resistin, chemerin, visfatin, vaspin, CXCL-12/SDF-1, angiotensinogen), inflammatory cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α, monocyte chemotactic protein [MCP-1]), and plasminogen activator inhibitor-1 were measured. Acute Physiology and Chronic Health Evaluation II score was evaluated on day 1, and Sequential Organ Failure Assessment (SOFA) score and Japanese Association for Acute Medicine (JAAM) and International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation (DIC) scores were assessed at the times of blood sampling.
Hierarchical clustering analysis showed the cluster formed by resistin, IL-6, IL-8, MCP-1, and IL-10 on days 1, 2, and 4 represented the cytokine network throughout the acute phase of sepsis. Each cytokine in this network was significantly associated with SOFA and JAAM DIC scores over the acute phase. A Cox proportional hazards model focusing on the acute phase showed a significant relation of these five cytokines with patient prognosis.
Adipocytokines and an inflammatory cytokine profile assessed over time in sepsis patients showed that resistin was involved in an inflammatory cytokine network including IL-6, IL-8, IL-10, and MCP-1 in the acute phase of sepsis, and this network was associated with severity and prognosis of sepsis.
细胞因子构成一个网络,在脓毒症的发病机制和预后中发挥关键作用。脂肪组织是一个释放脂肪细胞因子的重要免疫内分泌器官。本研究旨在从网络角度评估脓毒症中的脂肪细胞因子。
本回顾性研究纳入了2014年2月至2015年7月期间的37例脓毒症患者和12例健康对照。在第1天(诊断后24小时内)、第2天、第4天、第6天、第8天、第11天和第15天采集患者血样,并采集健康对照的血样。检测脂肪细胞因子(脂联素、瘦素、抵抗素、趋化素、内脂素、内脏脂肪素、CXCL-12/SDF-1、血管紧张素原)、炎性细胞因子(IL-1β、IL-4、IL-6、IL-8、IL-10、IL-12/IL-23p40、TNF-α、单核细胞趋化蛋白[MCP-1])和纤溶酶原激活物抑制剂-1。在第1天评估急性生理与慢性健康状况评分II,在采血时评估序贯器官衰竭评估(SOFA)评分、日本急性医学协会(JAAM)和国际血栓与止血协会显性弥散性血管内凝血(DIC)评分。
层次聚类分析显示,在第1天、第2天和第4天,由抵抗素、IL-6、IL-8、MCP-1和IL-10组成的聚类代表了脓毒症急性期的细胞因子网络。该网络中的每种细胞因子在急性期均与SOFA和JAAM DIC评分显著相关。关注急性期的Cox比例风险模型显示这五种细胞因子与患者预后存在显著关联。
对脓毒症患者随时间评估的脂肪细胞因子和炎性细胞因子谱显示,在脓毒症急性期,抵抗素参与了一个包括IL-6、IL-8、IL-10和MCP-1的炎性细胞因子网络,且该网络与脓毒症的严重程度和预后相关。