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König, Rainer
[VerfasserIn];
Kolte, Amol
[VerfasserIn];
Ahlers, Olaf
[VerfasserIn];
Oswald, Marcus
[VerfasserIn];
Krauß, Veiko
[VerfasserIn];
Röll, Daniela
[VerfasserIn];
Sommerfeld, Oliver
[VerfasserIn];
Dimopoulos, George
[VerfasserIn];
Tsangaris, Iraklis
[VerfasserIn];
Antoniadou, Eleni
[VerfasserIn];
Jaishankar, Neeraja
[VerfasserIn];
Bogatsch, Holger
[VerfasserIn];
Löffler, Markus
[VerfasserIn];
Rödel, Markus
[VerfasserIn];
Garcia-Moreno, Marina
[VerfasserIn];
Tuchscherr, Lorena
[VerfasserIn];
Sprung, Charles L.
[VerfasserIn];
Singer, Mervyn
[VerfasserIn];
Brunkhorst, Frank Martin
[VerfasserIn];
Oppert, Michael
[VerfasserIn];
Gerlach, Herwig
[VerfasserIn];
Claus, Ralf
[VerfasserIn];
Coldewey, Sina
[VerfasserIn];
Briegel, Josef
[VerfasserIn];
[...]
Use of IFNγ/IL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock
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- Medientyp: E-Artikel
- Titel: Use of IFNγ/IL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock
- Beteiligte: König, Rainer [VerfasserIn]; Kolte, Amol [VerfasserIn]; Ahlers, Olaf [VerfasserIn]; Oswald, Marcus [VerfasserIn]; Krauß, Veiko [VerfasserIn]; Röll, Daniela [VerfasserIn]; Sommerfeld, Oliver [VerfasserIn]; Dimopoulos, George [VerfasserIn]; Tsangaris, Iraklis [VerfasserIn]; Antoniadou, Eleni [VerfasserIn]; Jaishankar, Neeraja [VerfasserIn]; Bogatsch, Holger [VerfasserIn]; Löffler, Markus [VerfasserIn]; Rödel, Markus [VerfasserIn]; Garcia-Moreno, Marina [VerfasserIn]; Tuchscherr, Lorena [VerfasserIn]; Sprung, Charles L. [VerfasserIn]; Singer, Mervyn [VerfasserIn]; Brunkhorst, Frank Martin [VerfasserIn]; Oppert, Michael [VerfasserIn]; Gerlach, Herwig [VerfasserIn]; Claus, Ralf [VerfasserIn]; Coldewey, Sina [VerfasserIn]; Briegel, Josef [VerfasserIn]; Giamarellos-Bourboulis, Evangelos J. [VerfasserIn]; Keh, Didier [VerfasserIn]; Bauer, Michael [VerfasserIn]
- Erschienen: 09 March 2021
- Erschienen in: Frontiers in immunology ; 12(2021) Artikel-Nummer 607217, 11 Seiten
- Sprache: Englisch
- DOI: 10.3389/fimmu.2021.607217
- ISSN: 1664-3224
- Identifikator:
- Entstehung:
- Anmerkungen:
- Beschreibung: Large clinical trials testing hydrocortisone therapy in septic shock have produced conflicting results. Subgroups may benefit of hydrocortisone treatment depending on their individual immune response. We performed an exploratory analysis of the databasefrom the international randomized controlled clinical trial Corticosteroid Therapy of Septic Shock (CORTICUS) employing machine learning to a panel of 137 variables collected from the Berlin subcohort comprising 83 patients including demographic and clinical measures, organ failure scores, leukocyte counts and levels of circulating cytokines. The identified theranostic marker was validated against data from a cohort of the Hellenic Sepsis Study Group (HSSG) (n = 246), patients enrolled in the clinical trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT, n= 118), and another, smaller clinical trial (Crossover study, n = 20). In addition, in vitroblood culture experiments and in vivo experiments in mouse models were performed toassess biological plausibility. A low serum IFNγ/IL10 ratio predicted increased survival inthe hydrocortisone group whereas a high ratio predicted better survival in the placebogroup. Using this marker for a decision rule, we applied it to three validation sets andobserved the same trend. Experimental studies in vitro revealed that IFNγ/IL10 wasKönig et al. IFNγ/IL10 Ratio Stratifies Hydrocortisone Therapy negatively associated with the load of (heat inactivated) pathogens in spiked human blood and in septic mouse models. Accordingly, an in silico analysis of published IFNγ andIL10 values in bacteremic and non-bacteremic patients with the Systemic InflammatoryResponse Syndrome supported this association between the ratio and pathogen burden.We propose IFNγ/IL10 as a molecular marker supporting the decision to administerhydrocortisone to patients in septic shock. Prospective clinical studies are necessaryand standard operating procedures need to be implemented, particularly to define ageneric threshold. If confirmed, IFNγ/IL10 may become a suitable theranostic marker foran urging clinical need. Keywords: sepsis, hydrocortisone, immune therapy, machine learning, theranostics, steroids, IFNgamma/IL10
- Zugangsstatus: Freier Zugang