Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles.
Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles.
复制标题
DOI：
10.3389/fimmu.2020.621222
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
Ulrich MMW
中科院分区：
文献类型：
--
作者：
Mulder PPG;Vlig M;Boekema BKHL;Stoop MM;Pijpe A;van Zuijlen PPM;de Jong E;van Cranenbroek B;Joosten I;Koenen HJPM;Ulrich MMW
严重烧伤引起局部和全身免疫反应，可持续长达数月，并可导致全身炎症反应综合征，器官损伤和长期后遗症，如增生性瘢痕。为了预防这些病理状况，更好地了解潜在的机制是必不可少的。在这项纵向研究中，我们通过流式细胞术和分泌组分析了20名烧伤患者入住重症监护室的时间外周血免疫谱，并将其与20名健康受试者的数据进行了比较。患者队列显示全身性炎症体征，并测量到持续高水平的促炎可溶性介质，如IL-6、IL-8、MCP-1、MIP-1β和MIP-3α。使用无监督和有监督的流式细胞术技术，我们观察到中性粒细胞和单核细胞连续释放到血液中至少39天。伤后前3周外周血中未成熟中性粒细胞数量增加（烧伤后为0.1-2.8 × 106/ml，健康对照组为5 × 103/ml）。淋巴细胞总数没有增加，但效应T细胞和调节性T细胞的数量从第二周开始增加。在CD 4 + T细胞群中，发现CCR 4 + CCR 6-和CCR 4 + CCR 6+细胞数量增加。总之，这些数据表明，严重烧伤诱导了持续的先天性炎症反应，包括未成熟中性粒细胞的释放，T细胞组成向整体更促炎表型转变，从而持续全身炎症并增加继发性并发症的风险。
Severe burn injury causes local and systemic immune responses that can persist up to months, and can lead to systemic inflammatory response syndrome, organ damage and long-term sequalae such as hypertrophic scarring. To prevent these pathological conditions, a better understanding of the underlying mechanisms is essential. In this longitudinal study, we analyzed the temporal peripheral blood immune profile of 20 burn wound patients admitted to the intensive care by flow cytometry and secretome profiling, and compared this to data from 20 healthy subjects. The patient cohort showed signs of systemic inflammation and persistently high levels of pro-inflammatory soluble mediators, such as IL-6, IL-8, MCP-1, MIP-1β, and MIP-3α, were measured. Using both unsupervised and supervised flow cytometry techniques, we observed a continuous release of neutrophils and monocytes into the blood for at least 39 days. Increased numbers of immature neutrophils were present in peripheral blood in the first three weeks after injury (0.1–2.8 × 106/ml after burn vs. 5 × 103/ml in healthy controls). Total lymphocyte numbers did not increase, but numbers of effector T cells as well as regulatory T cells were increased from the second week onward. Within the CD4+ T cell population, elevated numbers of CCR4+CCR6- and CCR4+CCR6+ cells were found. Altogether, these data reveal that severe burn injury induced a persistent innate inflammatory response, including a release of immature neutrophils, and shifts in the T cell composition toward an overall more pro-inflammatory phenotype, thereby continuing systemic inflammation and increasing the risk of secondary complications.
登录
查看更多内容
影响因子：
2.7
作者：
Johansson, Joakim;Sjogren, Florence;Sjoberg, Folke
通讯作者：
Sjoberg, Folke
影响因子：
15.9
作者：
Kim, CH;Rott, L;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
2.7
作者：
Bergquist, Maria;Hastbacka, Johanna;Lipcsey, Miklos
通讯作者：
Lipcsey, Miklos
影响因子：
29.7
作者：
Josefowicz SZ;Lu LF;Rudensky AY
通讯作者：
Rudensky AY
影响因子：
5.5
作者：
Demaret, Julie;Venet, Fabienne;Monneret, Guillaume
通讯作者：
Monneret, Guillaume