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Immune mechanisms and potential therapeutic interventions for sepsis-induced adrenal gland inflammation

脓毒症引起的肾上腺炎症的免疫机制和潜在治疗干预措施

基本信息

批准号：
202068379
负责人：
Professor Dr. Stefan R. Bornstein, Ph.D.
金额：
--
依托单位：
Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie
依托单位国家：
德国
项目类别：
Clinical Research Units
财政年份：
2011
资助国家：
德国
起止时间：
2010-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/202068379?language=en
关键词：
Immune mechanisms potential therapeutic interventions

项目摘要

Systemic inflammation resulting from infections frequently culminates in fatal septic shock syndrome. An adequate adrenal stress response is critical to cope with this life-threatening situation. In many critically ill patients, this homeostatic activation of the adrenal gland hormone production is impaired, although the mechanisms are mostly unknown. In the previous funding period, we demonstrated that both endotoxemiaprovoked SIRS and cecal ligation and puncture (CLP)-induced sepsis lead to systemic and adrenal gland inflammation which was associated with rapid immune cell infiltration and onset of cellular death of adrenal cells. Furthermore, we engaged mice with tissue-specific inactivation of TLR signaling, enabling us to identify myeloid cells in the adrenal gland microenvironment as being crucially involved in hypothalamic-pituitary-adrenal (HPA) axis activation and adrenal inflammation. In the next funding period we plan to further study the importance of tissue-restricted TLR signaling, immune cell infiltration, mitochondria function and dysfunction in the adrenal gland inflammation and cell death. Finally, we will study the protective effect of novel anti-inflammatory and mitochondria-targeted therapeutic interventions in the resolution of adrenal inflammation and prevention of cell death. With these approaches we will better understand the underlying mechanisms involved in sepsis-mediated adrenal gland deregulation and identify novel therapeutic interventions in sepsis treatments.

由感染引起的全身性炎症经常以致命的败血性休克综合征而达到高潮。充分的肾上腺应激反应是至关重要的，以科普这种危及生命的情况。在许多重症患者中，这种肾上腺激素产生的稳态激活受损，尽管其机制大多未知。在之前的资助期间，我们证明了内毒素血症引起的SIRS和盲肠结扎穿孔（CLP）诱导的脓毒症均导致全身和肾上腺炎症，这与快速免疫细胞浸润和肾上腺细胞死亡有关。此外，我们让小鼠参与TLR信号的组织特异性失活，使我们能够鉴定肾上腺微环境中的髓样细胞，因为它们与下丘脑-垂体-肾上腺（HPA）轴激活和肾上腺炎症密切相关。在下一个资助期内，我们计划进一步研究组织限制性TLR信号传导、免疫细胞浸润、线粒体功能和功能障碍在肾上腺炎症和细胞死亡中的重要性。最后，我们将研究新的抗炎和靶向治疗干预措施在解决肾上腺炎症和预防细胞死亡中的保护作用。通过这些方法，我们将更好地了解脓毒症介导的肾上腺失调的潜在机制，并确定脓毒症治疗的新的治疗干预措施。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

人成人肾上腺髓质祖细胞的分离、表征和分化

DOI：
10.5966/sctm.2012-0022
发表时间：
2012
期刊：
STEM CELLS Translational Medicine
影响因子：
6
作者：
Santana MM;Chung KF;Vukicevic V;Rosmaninho-Salgado J;Kanczkowski W;Cortez V;Hackmann K;Bastos CA;Mota A;Schrock E;Bornstein SR;Cavadas C;Ehrhart-Bornstein M
通讯作者：
Ehrhart-Bornstein M

The role of adrenal gland microenvironment in the HPA axis function and dysfunction during sepsis