Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,351 bioRxiv papers from 296,699 authors.
Use of IFNγ/IL10 ratio for stratification of hydrocortisone therapy in patients with septic shock
Charles L Sprung,
Ralf A Claus,
Sina M Coldewey,
Evangelos J Giamarellos-Bourboulis,
Posted 21 Dec 2018
bioRxiv DOI: 10.1101/502864
Posted 21 Dec 2018
Background: Large clinical trials testing hydrocortisone therapy in septic shock have produced conflicting results. Subgroups may however benefit depending on their individual immune response. Methods: We performed an exploratory analysis of the CORTICUS trial database employing machine learning to a panel of 137 variables collected from 83 patients (60 survivors, 23 non-survivors) including demographic and clinical measures, organ failure scores, leukocyte counts and circulating cytokine levels. The identified biomarker was validated against data collected from patients enrolled into a cohort of the Hellenic Sepsis Study Group (HSSG) (n=162) and two data sets of two other clinical trials. Ex vivo studies were performed on this biomarker to assess a possible mechanistic role. Results: 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 ratio for a decision rule, we found significant improvement in survival in the groups of patients being in compliance with the prediction rule (discovery set: OR=3.03 [95% Cl: 1.05-8.75], P=0.031, validation set: OR=2.01 [95% CI: 1.04-3.88], P=0.026). Applying the rule to two further, smaller datasets showed the same tendency. Mechanistic studies revealed that IFNγ/IL10 was negatively associated with pathogen load in spiked human blood. An in silico analysis of published IFNγ and IL10 values in bacteremic and non-bacteremic SIRS patients supported this association between the ratio and pathogen burden. Conclusion: If confirmed prospectively, the IFNγ/IL10 ratio could be used as a rapidly available theranostic for use of hydrocortisone therapy in septic shock.
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