GSE106878 IFN γ/IL10 ratio stratifies corticosteroids therapy for septic shock

Contributors : Michael Bauer ; Amol Kolte ; Rainer K önigSeries Type : Expression profiling by arrayOrganism : Homo sapiensTo stratify hydrocortisone application in septic shock, we investigated an immune sub-study of the CORTICUS trial (Sprung et.al 2008, NEJM) employing machine learning to a panel of 120 parameters of 84 patients (n=24 non-survived, n=60 survived, 28 days) with special emphasis on potentially disadvantageous corticosteroids effects in the context of sepsis including clinical parameters, organ failure scores, lymphocyte counts and plasma protein concentrations of cytokines. We identified the ratio of IFN γ/IL10 in serum before randomization to serve as a valid biomarker for treatment stratification. This was validated with cytokine serum levels of patients (n=49) from the SISPCT study (Bloos et.al 2016, JAMA) and the early arm (n=20) of a hydrocortisone cross-over study (Keh et.al. 2003, Am J Respi r Crit Care Med). Integrating these three studies, we yielded an odds ratio of 2.1 and a 95% confidence interval of 0.99-4.52 (P=0.03).In vitro assays revealed IFNγ/Il10 to reflect the burden or severity of systemic infection. Severity was evidencedbyserum levels of these cy-tokines in the patients with septic shock we observed, and also in patients with less severe sepsis. Elucidating the molecular regulation of leukocytes during treatment and placebo by a transcriptomics analysis pointed to induced recovery of immune cell function due to hydro-cortisone t...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research