Collectively, these data demonstrate that a combination of IL-27 and PCT improves the overall ability to predict infection in this cohort of critically ill patients, compared with either biomarker contain alone.Figure 2Classification and regression tree (CART)-generated decision tree combining IL-27 and procalcitonin (PCT) for the prediction of bacterial infection in critically ill patients. Each node provides the total number of patients in either the sepsis (“Infected”) …DiscussionWe previously reported differential patterns of gene expression across the SIRS, sepsis, and septic-shock clinical spectrum [14]. In that previous study, however, the classifications of “sepsis” and “septic shock” were based on either laboratory confirmation of a pathogen, or high clinical suspicion of infection, according to published, pediatric specific criteria [19].
The current analysis is specifically targeted toward identification of patients with signs of inflammation and laboratory confirmation of a bacterial pathogen. Accordingly, all of the patients in the current study who met criteria for sepsis and septic shock also had laboratory confirmation of a bacterial pathogen.Based on this analytic approach, we leveraged the discovery potential of microarray-based transcriptomics and generated a list of genes differentially regulated between critically ill patients with SIRS (that is, patients with sterile systemic inflammation) and critically ill patients with sepsis (that is, patients with systemic inflammation secondary to a documented bacterial pathogen).
This gene list represents a potential working list of candidate diagnostic biomarkers for bacterial infection in critically ill patients. The global expression patterns of the top 100 class-predictor genes were able to predict SIRS and sepsis classes with high specificity and a high positive predictive value.Generating gene-expression data and gene-expression mosaics for 100 genes may not yet be clinically feasible within the time-sensitive constraints of the intensive care unit. Accordingly, we investigated the ability of serum IL-27 protein concentrations to predict bacterial infection in critically ill patients. The rationale for investigating IL-27 is based on the observation that EBI3 had the highest predictive strength for bacterial infection of all genes differentially regulated between patients with SIRS and patients with sepsis.
IL-27 is a heterodimeric cytokine belonging the IL-6 and IL-12 family of cytokines and is composed of the IL-27-p28 and EBI3 subunits, which are produced by antigen-presenting cells on exposure to microbial products and inflammatory Entinostat stimuli [27]. IL-27 is a regulator T-cells, having both pro- and antiinflammatory effects [28,29], and is rapidly induced in a murine model of septic peritonitis [30].