Koenig, R;
Kolte, A;
Ahlers, O;
Oswald, M;
Krauss, V;
Roell, D;
Sommerfeld, O;
... Bauer, M; + view all
(2021)
Use of IFN gamma/IL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock.
Frontiers in Immunology
, 12
, Article 607217. 10.3389/fimmu.2021.607217.
Preview |
Text
Use of IFNγIL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock.pdf - Published Version Download (738kB) | Preview |
Abstract
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 database from 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 vitro blood culture experiments and in vivo experiments in mouse models were performed to assess biological plausibility. A low serum IFNγ/IL10 ratio predicted increased survival in the hydrocortisone group whereas a high ratio predicted better survival in the placebo group. Using this marker for a decision rule, we applied it to three validation sets and observed the same trend. Experimental studies in vitro revealed that IFNγ/IL10 was 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 and IL10 values in bacteremic and non-bacteremic patients with the Systemic Inflammatory Response Syndrome supported this association between the ratio and pathogen burden. We propose IFNγ/IL10 as a molecular marker supporting the decision to administer hydrocortisone to patients in septic shock. Prospective clinical studies are necessary and standard operating procedures need to be implemented, particularly to define a generic threshold. If confirmed, IFNγ/IL10 may become a suitable theranostic marker for an urging clinical need.
| Type: | Article |
|---|---|
| Title: | Use of IFN gamma/IL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2021.607217 |
| Publisher version: | http://dx.doi.org/10.3389/fimmu.2021.607217 |
| Language: | English |
| Additional information: | Copyright © 2021 König, Kolte, Ahlers, Oswald, Krauss, Roell, Sommerfeld, Dimopoulos, Tsangaris, Antoniadou, Jaishankar, Bogatsch, Löffler, Rödel, Garcia-Moreno, Tuchscherr, Sprung, Singer, Brunkhorst, Oppert, Gerlach, Claus, Coldewey, Briegel, Giamarellos-Bourboulis, Keh and Bauer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | sepsis, hydrocortisone, immune therapy, machine learning, theranostics, steroids, IFNgamma, IL10 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10128588 |
Archive Staff Only
 |
View Item |
