{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:46:24Z","timestamp":1791924384122,"version":"4.3.4"},"reference-count":110,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Septic shock is a life-threatening condition caused by microorganisms and their toxins, which often results in severe haemodynamic instability and multi-organ dysfunction. Immune system dysfunction and endothelial injury play crucial roles in its pathogenesis and progression. In septic shock, pathogen recognition triggers immune activation, leading to excessive cytokine release and hyperactivation of immune cells. This overwhelming inflammatory response not only exacerbates endothelial injury, but also increases the risk of secondary infections, creating a vicious cycle that suppresses immune function and increases mortality. Cytokines alter the endothelial cell phenotype and structure, causing dysfunction, increased vascular permeability, and infiltration of inflammatory cells and cytokines into the interstitial space. The exposure of adhesion molecules promotes leukocyte migration and activation of coagulation pathways, significantly increasing the risk of thrombosis. These interactions contribute towards systemic oedema, hypotension, and microcirculatory dysfunction, exacerbating organ hypoxia and failure. This article explores the intricate interplay between endothelial injury and immune response in septic shock and its clinical implications. We highlight the potential of immunomodulation in mitigating immune damage as well as suppression. Additionally, we discuss endothelium-targeted therapies, including anti-inflammatory strategies, endothelial repair, and microcirculation improvement. Future research should focus on developing novel drugs and refining therapeutic approaches to effectively counteract endothelial damage and immune dysregulation, ultimately improving clinical outcomes and reducing morbidity and mortality.<\/jats:p>","DOI":"10.3389\/fphys.2025.1627008","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T05:34:18Z","timestamp":1756964058000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Interaction between endothelial injury and immune response in septic shock: from basic research to clinical applications"],"prefix":"10.3389","volume":"16","author":[{"given":"Yang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Nan","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-Jv","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Meng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e42190","DOI":"10.1097\/MD.0000000000042190","article-title":"Outcomes of patients with sepsis due extensively drug-resistant bacterial infections with and without polyspecific intravenous immunoglobulin therapy: a retrospective study","volume":"104","author":"Acar","year":"2025","journal-title":"Med. Baltim."},{"key":"B2","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1007\/s10753-016-0500-6","article-title":"Alteration of lysophosphatidylcholine-related metabolic parameters in the plasma of mice with experimental sepsis","volume":"40","author":"Ahn","year":"2017","journal-title":"Inflammation"},{"key":"B3","doi-asserted-by":"publisher","first-page":"H647","DOI":"10.1152\/ajpheart.00090.2018","article-title":"Role of matrix metalloproteinases and histone deacetylase in oxidative stress-induced degradation of the endothelial glycocalyx","volume":"316","author":"Ali","year":"2019","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1111\/anae.12661","article-title":"The endothelial glycocalyx: a review of the vascular barrier","volume":"69","author":"Alphonsus","year":"2014","journal-title":"Anaesthesia"},{"key":"B5","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.bja.2021.10.039","article-title":"Reduction of NETosis by targeting CXCR1\/2 reduces thrombosis, lung injury, and mortality in experimental human and murine sepsis","volume":"128","author":"Alsabani","year":"2022","journal-title":"Br. J. Anaesth."},{"key":"B6","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1097\/ACO.0000000000000963","article-title":"Pathophysiology of sepsis","volume":"34","author":"Arina","year":"2021","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"B111","first-page":"32","article-title":"What do you need to know about patients on admission to manage their behaviors safely?","volume":"27","year":"1989","journal-title":"J. Psychosoc. Nurs. Ment. Health Serv."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4217","DOI":"10.2147\/JIR.S363693","article-title":"Extracellular histones activate endothelial NLRP3 inflammasome and are associated with a severe sepsis phenotype","volume":"15","author":"Beltran-Garcia","year":"","journal-title":"J. Inflamm. Res."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10030525","article-title":"Characterization of early peripheral immune responses in patients with sepsis and septic shock","volume":"10","author":"Beltran-Garcia","year":"","journal-title":"Biomedicines"},{"key":"B9","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1177\/08850666251331905","article-title":"Real-world outcomes of hemoadsorption with CytoSorb((R)) in patients with septic shock: insights from a single-center study","volume":"40","author":"Berlot","year":"2025","journal-title":"J. Intensive Care Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1016877","DOI":"10.3389\/fimmu.2022.1016877","article-title":"Neonatal sepsis and transient immunodeficiency: potential for novel immunoglobulin therapies?","volume":"13","author":"Beudeker","year":"2022","journal-title":"Front. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/jcp.21505","article-title":"Lipopolysaccharide plus hypoxia and reoxygenation synergistically reduce electrical coupling between microvascular endothelial cells by dephosphorylating connexin40","volume":"217","author":"Bolon","year":"2008","journal-title":"J. Cell Physiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e10128","DOI":"10.15252\/emmm.201810128","article-title":"Sepsis therapies: learning from 30 years of failure of translational research to propose new leads","volume":"12","author":"Cavaillon","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12959-019-0198-4","article-title":"Sepsis and septic shock: endothelial molecular pathogenesis associated with vascular microthrombotic disease","volume":"17","author":"Chang","year":"2019","journal-title":"Thromb. J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"108742","DOI":"10.1016\/j.clim.2021.108742","article-title":"PD-1 signaling pathway in sepsis: does it have a future?","volume":"229","author":"Chen","year":"2021","journal-title":"Clin. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/ni.3398","article-title":"Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis","volume":"17","author":"Cheng","year":"2016","journal-title":"Nat. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/nm1565","article-title":"Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood","volume":"13","author":"Clark","year":"2007","journal-title":"Nat. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1142\/S0192415X14500761","article-title":"Effect of rhubarb pre-treatment on intestinal microcirculation in septic rats","volume":"42","author":"Cui","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.4103\/0366-6999.185859","article-title":"Rhubarb antagonizes matrix metalloproteinase-9-induced vascular endothelial permeability","volume":"129","author":"Cui","year":"2016","journal-title":"Chin. Med. J. Engl."},{"key":"B19","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1097\/CCM.0b013e3182742e8b","article-title":"Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome","volume":"41","author":"De Backer","year":"2013","journal-title":"Crit. Care Med."},{"key":"B20","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1080\/10428194.2022.2100367","article-title":"The impact of tocilizumab treatment for cytokine release syndrome on the incidence of early blood stream infections after peripheral blood haploidentical hematopoietic cell transplantation","volume":"63","author":"De Togni","year":"2022","journal-title":"Leuk. Lymphoma"},{"key":"B21","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/j.immuni.2018.08.016","article-title":"The endotoxin delivery protein HMGB1 mediates caspase-11-dependent lethality in sepsis","volume":"49","author":"Deng","year":"2018","journal-title":"Immunity"},{"key":"B22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3389\/fphys.2019.00011","article-title":"The systemic alterations of lipids, alanine-glucose cycle and inter-organ amino acid metabolism in swine model confirms the role of liver in early Phase of septic shock","volume":"10","author":"Ferrario","year":"2019","journal-title":"Front. Physiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.mcna.2020.02.011","article-title":"Sepsis and Septic Shock - basics of diagnosis, pathophysiology and clinical decision making","volume":"104","author":"Font","year":"2020","journal-title":"Med. Clin. North Am."},{"key":"B24","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.jtha.2023.09.028","article-title":"Trauma-induced innate immune activation and disseminated intravascular coagulation","volume":"22","author":"Gando","year":"2024","journal-title":"J. Thromb. Haemost."},{"key":"B25","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.cmi.2016.01.021","article-title":"Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins","volume":"22","author":"Giamarellos-Bourboulis","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"B26","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/ni.3324","article-title":"New insights into the multidimensional concept of macrophage ontogeny, activation and function","volume":"17","author":"Ginhoux","year":"2016","journal-title":"Nat. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1007\/s00134-024-07586-2","article-title":"Understanding, assessing and treating immune, endothelial and haemostasis dysfunctions in bacterial sepsis","volume":"50","author":"Girardis","year":"2024","journal-title":"Intensive Care Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1055\/a-1813-2057","article-title":"Pathophysiology of sepsis","volume":"58","author":"Gregorius","year":"2023","journal-title":"Anasthesiol Intensivmed. Notfallmed Schmerzther"},{"key":"B29","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/imm.12854","article-title":"The biology of natural killer cells during sepsis","volume":"153","author":"Guo","year":"2018","journal-title":"Immunology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.intimp.2015.10.026","article-title":"Ulinastatin- and thymosin alpha1-based immunomodulatory strategy for sepsis: a meta-analysis","volume":"29","author":"Han","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/cr.2011.13","article-title":"NF-kappaB in immunobiology","volume":"21","author":"Hayden","year":"2011","journal-title":"Cell Res."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910238","article-title":"Renal replacement techniques in septic shock","volume":"22","author":"Hellman","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"538 e9","DOI":"10.1016\/j.jcrc.2012.11.022","article-title":"Severe abnormalities in microvascular perfused vessel density are associated to organ dysfunctions and mortality and can be predicted by hyperlactatemia and norepinephrine requirements in septic shock patients","volume":"28","author":"Hernandez","year":"2013","journal-title":"J. Crit. Care"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1056\/NEJMcibr1917242","article-title":"Activating immunity to fight a foe - a new path","volume":"382","author":"Hotchkiss","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/nri3552","article-title":"Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1016\/j.ymthe.2021.12.013","article-title":"Tim-3 regulates sepsis-induced immunosuppression by inhibiting the NF-kappaB signaling pathway in CD4 T cells","volume":"30","author":"Huang","year":"2022","journal-title":"Mol. Ther."},{"key":"B37","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1097\/SHK.0000000000000473","article-title":"The endothelium in sepsis","volume":"45","author":"Ince","year":"2016","journal-title":"Shock"},{"key":"B38","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1164\/rccm.201910-1911TR","article-title":"Endothelial responses in sepsis","volume":"202","author":"Joffre","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.20696.1","article-title":"Developing better drugs for pulmonary sarcoidosis: determining indications for treatment and endpoints to assess therapy based on patient and clinician concerns","volume":"8","author":"Judson","year":"2019","journal-title":"F1000Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"22351","DOI":"10.1073\/pnas.2010229117","article-title":"IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome","volume":"117","author":"Kang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B41","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe7729","article-title":"Neutrophils self-limit swarming to contain bacterial growth in vivo","volume":"372","author":"Kienle","year":"2021","journal-title":"Science"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13010294","article-title":"Impact of CytoSorb hemoadsorption therapy on fluid balance in patients with septic shock","volume":"13","author":"Kogelmann","year":"2024","journal-title":"J. Clin. Med."},{"key":"B44","article-title":"Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis","author":"Kun Yang","year":"2022"},{"key":"B45","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nri2936","article-title":"Emerging inflammasome effector mechanisms","volume":"11","author":"Lamkanfi","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3759","DOI":"10.7150\/thno.20734","article-title":"Dual functioned pegylated phospholipid micelles containing cationic antimicrobial decapeptide for treating sepsis","volume":"7","author":"Lee","year":"2017","journal-title":"Theranostics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1186\/s13063-020-04549-y","article-title":"The I-MICRO trial, Ilomedin for treatment of septic shock with persistent microperfusion defects: a double-blind, randomized controlled trial-study protocol for a randomized controlled trial","volume":"21","author":"Legrand","year":"2020","journal-title":"Trials"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1164\/rccm.202410-1924OC","article-title":"Iloprost for the treatment of severe septic shock with persistent hypoperfusion: a double-blind, randomized controlled trial","volume":"211","author":"Legrand","year":"2025","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.ijid.2014.12.032","article-title":"Thymosin alpha1 based immunomodulatory therapy for sepsis: a systematic review and meta-analysis","volume":"33","author":"Li","year":"2015","journal-title":"Int. J. Infect. Dis."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imlet.2015.11.009","article-title":"The immunoprotective activity of interleukin-33 in mouse model of cecal ligation and puncture-induced sepsis","volume":"169","author":"Li","year":"2016","journal-title":"Immunol. Lett."},{"key":"B51","doi-asserted-by":"publisher","first-page":"L622","DOI":"10.1152\/ajplung.00477.2005","article-title":"NF-kappa B activation as a pathological mechanism of septic shock and inflammation","volume":"290","author":"Liu","year":"2006","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s40779-022-00422-y","article-title":"Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options","volume":"9","author":"Liu","year":"2022","journal-title":"Mil. Med. Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1089\/jir.2014.0235","article-title":"Effect of regulatory T cells on promoting apoptosis of T lymphocyte and its regulatory mechanism in sepsis","volume":"35","author":"Luan","year":"2015","journal-title":"J. Interferon Cytokine Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.3389\/fimmu.2019.01037","article-title":"Role of neutrophil extracellular traps and vesicles in regulating vascular endothelial permeability","volume":"10","author":"Ma","year":"2019","journal-title":"Front. Immunol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"175","DOI":"10.2174\/187153006777442369","article-title":"Coagulation and sepsis","volume":"6","author":"Machado","year":"2006","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"B56","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMoa022139","article-title":"The epidemiology of sepsis in the United States from 1979 through 2000","author":"Martin","year":"2003"},{"key":"B57","doi-asserted-by":"publisher","first-page":"155","DOI":"10.3389\/fimmu.2015.00155","article-title":"Pro-coagulant endothelial dysfunction results from EHEC shiga toxins and host damage-associated molecular patterns","volume":"6","author":"Mayer","year":"2015","journal-title":"Front. Immunol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1182\/blood-2016-09-741298","article-title":"Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice","volume":"129","author":"McDonald","year":"2017","journal-title":"Blood"},{"key":"B59","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1161\/CIRCRESAHA.120.317447","article-title":"The emerging threat of (Micro)Thrombosis in COVID-19 and its therapeutic implications","volume":"127","author":"McFadyen","year":"2020","journal-title":"Circ. Res."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8010070","article-title":"CTLA-4 genetic variants predict survival in patients with sepsis","volume":"8","author":"Mewes","year":"2019","journal-title":"J. Clin. Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.atherosclerosis.2008.03.024","article-title":"Tumor necrosis factor-alpha inhibition protects against endotoxin-induced endothelial glycocalyx perturbation","volume":"202","author":"Nieuwdorp","year":"2009","journal-title":"Atherosclerosis"},{"key":"B62","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/joim.12331","article-title":"Endothelial barrier dysfunction in septic shock","volume":"277","author":"Opal","year":"2015","journal-title":"J. Intern Med."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.202501-012OC","article-title":"Endothelial glycocalyx degradation in sepsis: analysis of the crystalloid liberal or vasopressors early resuscitation in sepsis (CLOVERS) trial, a multicenter, Phase 3, randomized trial","author":"Oshima","year":"2025","journal-title":"Ann. Am. Thorac. Soc"},{"key":"B64","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.cyto.2015.02.013","article-title":"Evaluation of endothelial biomarkers as predictors of organ failures in septic shock patients","volume":"73","author":"Palud","year":"2015","journal-title":"Cytokine"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.4103\/0366-6999.231524","article-title":"Role of combining peripheral with sublingual perfusion on evaluating microcirculation and predicting prognosis in patients with septic shock","volume":"131","author":"Pan","year":"2018","journal-title":"Chin. Med. J. Engl."},{"key":"B66","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1038\/s41419-022-05264-z","article-title":"Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis","volume":"13","author":"Pan","year":"2022","journal-title":"Cell Death Dis."},{"key":"B67","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1164\/rccm.201603-0596OC","article-title":"Autophagy primes neutrophils for neutrophil extracellular trap formation during sepsis","volume":"196","author":"Park","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B68","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.ccc.2019.12.001","article-title":"Immune consequences of endothelial cells' activation and dysfunction during sepsis","volume":"36","author":"Pons","year":"2020","journal-title":"Crit. Care Clin."},{"key":"B69","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00063-023-01028-5","article-title":"What is new and different in the 2021 Surviving Sepsis Campaign guidelines","volume":"118","author":"Prescott","year":"2023","journal-title":"Med. Klin. Intensivmed. Notfmed"},{"key":"B70","doi-asserted-by":"publisher","first-page":"109561","DOI":"10.1016\/j.intimp.2022.109561","article-title":"PLD2 deletion alleviates disruption of tight junctions in sepsis-induced ALI by regulating PA\/STAT3 phosphorylation pathway","volume":"114","author":"Qian","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1093\/bja\/aes321","article-title":"Role of microparticles in sepsis","volume":"109","author":"Reid","year":"2012","journal-title":"Br. J. Anaesth."},{"key":"B72","doi-asserted-by":"publisher","first-page":"110610","DOI":"10.1016\/j.intimp.2023.110610","article-title":"Exploring dysregulated immune response genes and endothelial dysfunction biomarkers as predictors of severe COVID-19","volume":"122","author":"Reis-Goes","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/j.cmi.2020.05.030","article-title":"Tuberculosis sepsis after tocilizumab treatment","volume":"26","author":"Reisinger","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"B74","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1038\/414920a","article-title":"MIF regulates innate immune responses through modulation of Toll-like receptor 4","volume":"414","author":"Roger","year":"2001","journal-title":"Nature"},{"key":"B75","doi-asserted-by":"publisher","first-page":"H2247","DOI":"10.1152\/ajpheart.00796.2005","article-title":"Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury","volume":"290","author":"Rubio-Gayosso","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8120539","article-title":"Hemoadsorption with CytoSorb in septic shock reduces catecholamine requirements and in-hospital mortality: a single-center retrospective 'genetic' matched analysis","volume":"8","author":"Rugg","year":"2020","journal-title":"Biomedicines"},{"key":"B77","article-title":"A randomized, controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsis","author":"Satoshi Gando","year":"2013"},{"key":"B78","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s40635-021-00383-x","article-title":"Sepsis: deriving biological meaning and clinical applications from high-dimensional data","volume":"9","author":"Schuurman","year":"2021","journal-title":"Intensive Care Med. Exp."},{"key":"B79","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1001\/jama.2016.0289","article-title":"Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Shankar-Hari","year":"2016","journal-title":"JAMA"},{"key":"B80","doi-asserted-by":"publisher","first-page":"3384","DOI":"10.1038\/s41467-020-17153-0","article-title":"A nanotrap improves survival in severe sepsis by attenuating hyperinflammation","volume":"11","author":"Shi","year":"2020","journal-title":"Nat. Commun."},{"key":"B81","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1007\/s15010-023-02082-z","article-title":"Trends in mortality after a sepsis hospitalization: a nationwide prospective registry study from 2008 to 2021","volume":"51","author":"Skei","year":"2023","journal-title":"Infection"},{"key":"B83","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1097\/01.ccm.0000155991.88802.4d","article-title":"Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock","volume":"33","author":"Sunden-Cullberg","year":"2005","journal-title":"Crit. Care Med."},{"key":"B84","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/s41422-019-0164-5","article-title":"The molecular machinery of regulated cell death","volume":"29","author":"Tang","year":"2019","journal-title":"Cell Res."},{"key":"B85","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1097\/TP.0000000000003060","article-title":"Liposomal delivery improves the efficacy of prednisolone to attenuate renal inflammation in a mouse model of acute renal allograft rejection","volume":"104","author":"van Alem","year":"2020","journal-title":"Transplantation"},{"key":"B86","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1164\/rccm.201308-1535OC","article-title":"Simultaneous targeting of IL-1 and IL-18 is required for protection against inflammatory and septic shock","volume":"189","author":"Vanden Berghe","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B87","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrneph.2017.165","article-title":"Advances in the understanding and treatment of sepsis-induced immunosuppression","volume":"14","author":"Venet","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"100109","DOI":"10.1016\/j.ccrj.2025.100109","article-title":"A gene expression-based approach for the precision use of hydrocortisone in septic shock patients; a secondary analysis of the ADRENAL trial","volume":"27","author":"Venkatesh","year":"2025","journal-title":"Crit. Care Resusc."},{"key":"B89","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1186\/cc3748","article-title":"Microvascular dysfunction as a cause of organ dysfunction in severe sepsis","volume":"9","author":"Vincent","year":"2005","journal-title":"Crit. Care"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11195782","article-title":"Biomarkers for the prediction and judgement of sepsis and sepsis complications: a step towards precision medicine?","volume":"11","author":"von Groote","year":"2022","journal-title":"J. Clin. Med."},{"key":"B91","doi-asserted-by":"crossref","first-page":"6733465","DOI":"10.1155\/2023\/6733465","article-title":"IV vitamin C in sepsis: a latest systematic review and meta-analysis","volume":"2023","author":"Wen","year":"2023","journal-title":"Int. J. Clin. Pract."},{"key":"B92","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ejphar.2013.01.024","article-title":"Sepsis-induced leukocyte adhesion in the pulmonary microvasculature in vivo is mediated by CD11a and CD11b","volume":"702","author":"Wang","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"e9859","DOI":"10.1097\/MD.0000000000009859","article-title":"Caspase-1-dependent pyroptosis of peripheral blood mononuclear cells predicts the development of sepsis in severe trauma patients: a prospective observational study","volume":"97","author":"Wang","year":"2018","journal-title":"Med. Baltim."},{"key":"B94","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1146\/annurev.bioeng.9.060906.151959","article-title":"The structure and function of the endothelial glycocalyx layer","volume":"9","author":"Weinbaum","year":"2007","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"B95","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.bbrc.2019.01.090","article-title":"The release and activity of HMGB1 in ferroptosis","volume":"510","author":"Wen","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B96","doi-asserted-by":"publisher","first-page":"36","DOI":"10.4161\/viru.25436","article-title":"Host innate immune responses to sepsis","volume":"5","author":"Wiersinga","year":"2014","journal-title":"Virulence"},{"key":"B97","doi-asserted-by":"publisher","first-page":"e0275632","DOI":"10.1371\/journal.pone.0275632","article-title":"Resveratrol therapy improves liver function via estrogen-receptors after hemorrhagic shock in rats","volume":"17","author":"Wolf","year":"2022","journal-title":"PLoS One"},{"key":"B98","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1097\/SHK.0000000000001345","article-title":"Norepinephrine vs vasopressin: which vasopressor should Be discontinued first in septic shock? A meta-analysis","volume":"53","author":"Wu","year":"2020","journal-title":"Shock"},{"key":"B99","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.1084\/jem.20111354","article-title":"A genomic storm in critically injured humans","volume":"208","author":"Xiao","year":"2011","journal-title":"J. Exp. Med."},{"key":"B100","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.burns.2024.01.009","article-title":"Adenosine diphosphate ribosylation factor 6 inhibition protects burn sepsis induced lung injury through preserving vascular integrity and suppressing ASC inflammasome transmission","volume":"50","author":"Xiao","year":"2024","journal-title":"Burns"},{"key":"B101","doi-asserted-by":"publisher","first-page":"e2416904","DOI":"10.1002\/advs.202416904","article-title":"Annexin A3 represses endothelial permeability and inflammation during sepsis via actin cytoskeleton modulation","volume":"12","author":"Xing","year":"2025","journal-title":"Adv. Sci. (Weinh)"},{"key":"B102","doi-asserted-by":"publisher","first-page":"1172892","DOI":"10.3389\/fimmu.2023.1172892","article-title":"Sulodexide improves vascular permeability via glycocalyx remodelling in endothelial cells during sepsis","volume":"14","author":"Ying","year":"2023","journal-title":"Front. Immunol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1186\/s12931-023-02594-0","article-title":"Deficiency of S100A8\/A9 attenuates pulmonary microvascular leakage in septic mice","volume":"24","author":"Yu","year":"2023","journal-title":"Respir. Res."},{"key":"B104","doi-asserted-by":"publisher","first-page":"566","DOI":"10.3389\/fimmu.2020.00566","article-title":"Endothelial HSPA12B exerts protection against sepsis-induced severe cardiomyopathy via suppression of adhesion molecule expression by miR-126","volume":"11","author":"Zhang","year":"","journal-title":"Front. Immunol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"940","DOI":"10.3389\/fphar.2020.00940","article-title":"Efficacy and safety of recombinant human thrombopoietin on sepsis patients with thrombocytopenia: a systematic review and meta-analysis","volume":"11","author":"Zhang","year":"","journal-title":"Front. Pharmacol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"e1170","DOI":"10.1002\/ctm2.1170","article-title":"Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis","volume":"13","author":"Zhang","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"B107","doi-asserted-by":"publisher","first-page":"eadt7589","DOI":"10.1126\/sciadv.adt7589","article-title":"Endothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis","volume":"11","author":"Zhang","year":"2025","journal-title":"Sci. Adv."},{"key":"B108","doi-asserted-by":"publisher","first-page":"110992","DOI":"10.1016\/j.intimp.2023.110992","article-title":"PAR1 regulates sepsis-induced vascular endothelial barrier dysfunction by mediating ERM phosphorylation via the RhoA\/ROCK signaling pathway","volume":"124","author":"Zhao","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"2912","DOI":"10.1016\/j.asjsur.2023.02.004","article-title":"Efficacy and safety of glucocorticoid in the treatment of sepsis: a systematic review and meta-analysis","volume":"46","author":"Zou","year":"2023","journal-title":"Asian J. Surg."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2025.1627008\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T05:34:20Z","timestamp":1756964060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2025.1627008\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,4]]},"references-count":110,"alternative-id":["10.3389\/fphys.2025.1627008"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2025.1627008","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,4]]},"article-number":"1627008"}}