Matthijs Kox,Michael Bauer,Lieuwe D J Bos,Hjalmar Bouma,Thierry Calandra,Carolyn S Calfee,Benjamin G Chousterman,Lennie P G Derde,Evangelos J Giamarellos-Bourboulis,Hernando Gómez,Mihai G Netea,Marlies Ostermann,Tom van der Poll,Brendon P Scicluna,Christopher Seymour,Manu Shankar-Hari,Nathan Shapiro,Mervyn Singer,Fabienne Venet,Alexander P J Vlaar,Lonneke A van Vught,Sebastian Weis,W Joost Wiersinga,Peter Pickkers
{"title":"败血症的免疫学:将新见解转化为临床实践。","authors":"Matthijs Kox,Michael Bauer,Lieuwe D J Bos,Hjalmar Bouma,Thierry Calandra,Carolyn S Calfee,Benjamin G Chousterman,Lennie P G Derde,Evangelos J Giamarellos-Bourboulis,Hernando Gómez,Mihai G Netea,Marlies Ostermann,Tom van der Poll,Brendon P Scicluna,Christopher Seymour,Manu Shankar-Hari,Nathan Shapiro,Mervyn Singer,Fabienne Venet,Alexander P J Vlaar,Lonneke A van Vught,Sebastian Weis,W Joost Wiersinga,Peter Pickkers","doi":"10.1038/s41581-025-01004-6","DOIUrl":null,"url":null,"abstract":"Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Treatments that influence this dysregulated host response are sparse. The immunopathophysiology of sepsis entails overzealous inflammation causing acute organ dysfunction, as well as a profound and/or persistent anti-inflammatory response that increases susceptibility to secondary infection. The immune response in sepsis is under the influence of various endogenous and exogenous factors, including genetic makeup, age, sex, comorbidities, metabolism, prior microbial exposure and medications. The consequent heterogeneity of the syndrome hampers immunomodulatory treatment strategies that rely on a 'one-size-fits-all' approach. A precision medicine approach is therefore warranted. Balanced application of prognostic- and predictive-enrichment strategies is instrumental to achieve precision medicine. Phenotyping of patients using clinical, physiological, microbiological and/or molecular ('omics') data enables the identification of more homogeneous patient subgroups. Several studies suggest that such approaches can be used to tailor adjunctive immunomodulatory therapies in patients with sepsis. As well as repurposing existing drugs to treat sepsis, new drugs aimed at restoring immune homeostasis are under investigation. New clinical trial methodologies, including flexible platform trials, Bayesian statistics and embedding trials in health care systems are increasingly being used to keep pace with rapid developments in the field of sepsis immunobiology and ultimately to improve clinical outcomes.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"3 1","pages":""},"PeriodicalIF":39.8000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The immunology of sepsis: translating new insights into clinical practice.\",\"authors\":\"Matthijs Kox,Michael Bauer,Lieuwe D J Bos,Hjalmar Bouma,Thierry Calandra,Carolyn S Calfee,Benjamin G Chousterman,Lennie P G Derde,Evangelos J Giamarellos-Bourboulis,Hernando Gómez,Mihai G Netea,Marlies Ostermann,Tom van der Poll,Brendon P Scicluna,Christopher Seymour,Manu Shankar-Hari,Nathan Shapiro,Mervyn Singer,Fabienne Venet,Alexander P J Vlaar,Lonneke A van Vught,Sebastian Weis,W Joost Wiersinga,Peter Pickkers\",\"doi\":\"10.1038/s41581-025-01004-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Treatments that influence this dysregulated host response are sparse. The immunopathophysiology of sepsis entails overzealous inflammation causing acute organ dysfunction, as well as a profound and/or persistent anti-inflammatory response that increases susceptibility to secondary infection. The immune response in sepsis is under the influence of various endogenous and exogenous factors, including genetic makeup, age, sex, comorbidities, metabolism, prior microbial exposure and medications. The consequent heterogeneity of the syndrome hampers immunomodulatory treatment strategies that rely on a 'one-size-fits-all' approach. A precision medicine approach is therefore warranted. Balanced application of prognostic- and predictive-enrichment strategies is instrumental to achieve precision medicine. Phenotyping of patients using clinical, physiological, microbiological and/or molecular ('omics') data enables the identification of more homogeneous patient subgroups. 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The immunology of sepsis: translating new insights into clinical practice.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Treatments that influence this dysregulated host response are sparse. The immunopathophysiology of sepsis entails overzealous inflammation causing acute organ dysfunction, as well as a profound and/or persistent anti-inflammatory response that increases susceptibility to secondary infection. The immune response in sepsis is under the influence of various endogenous and exogenous factors, including genetic makeup, age, sex, comorbidities, metabolism, prior microbial exposure and medications. The consequent heterogeneity of the syndrome hampers immunomodulatory treatment strategies that rely on a 'one-size-fits-all' approach. A precision medicine approach is therefore warranted. Balanced application of prognostic- and predictive-enrichment strategies is instrumental to achieve precision medicine. Phenotyping of patients using clinical, physiological, microbiological and/or molecular ('omics') data enables the identification of more homogeneous patient subgroups. Several studies suggest that such approaches can be used to tailor adjunctive immunomodulatory therapies in patients with sepsis. As well as repurposing existing drugs to treat sepsis, new drugs aimed at restoring immune homeostasis are under investigation. New clinical trial methodologies, including flexible platform trials, Bayesian statistics and embedding trials in health care systems are increasingly being used to keep pace with rapid developments in the field of sepsis immunobiology and ultimately to improve clinical outcomes.
期刊介绍:
Nature Reviews Nephrology aims to be the premier source of reviews and commentaries for the scientific communities it serves.
It strives to publish authoritative, accessible articles.
Articles are enhanced with clearly understandable figures, tables, and other display items.
Nature Reviews Nephrology publishes Research Highlights, News & Views, Comments, Reviews, Perspectives, and Consensus Statements.
The content is relevant to nephrologists and basic science researchers.
The broad scope of the journal ensures that the work reaches the widest possible audience.