Predictive Value of IL-8 for Sepsis and Severe Infections After Burn Injury: A Clinical Study

Abstract

The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring postburn inflammation is of paramount importance but, so far, there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As interleukin 8 (IL-8) is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict postburn sepsis, infections, and mortality. Plasma cytokines, acute-phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days after injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure [MOF], and mortality) were recorded. A cutoff level for IL-8 was determined using receiver operating characteristic analysis. Statistical significance is set at P < 0.05. Receiver operating characteristic analysis identified a cutoff level of 234 pg/mL for IL-8 for survival. Patients were grouped according to their average IL-8 levels relative to this cutoff and stratified into high (H) (n = 133) and low (L) (n = 335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area burned and incidence of MOF (P < 0.001). In the H group, IL-8 levels were able to predict sepsis (P < 0.002). In the H group, elevated IL-8 was associated with increased inflammatory and acute-phase responses compared with the L group (P < 0.05). High levels of IL-8 correlated with increased MOF, sepsis, and mortality. These data suggest that serum levels of IL-8 may be a valid biomarker for monitoring sepsis, infections, and mortality in burn patients.

Trial registration: ClinicalTrials.gov NCT00675714.

Figures

Figure 1. Cut-off determination using receiver operating characteristic (ROC) analysis

Cut-off value at the intersection of sensitivity and specificity (A). Validated by ROC curve with A=0.88 (B).

Figure 2. Kaplan Meier survival curve for the observed first 60 days after burn injury

There is a significant higher mortality rate in the high IL-8 level group.

Figure 3. Pro-inflammatory Cytokines and Chemokines

IL-8 expression pattern shown over time (A). IL-1beta and IL-6 expression stratified based on IL-8 expression (B, C).

Figure 4. Forward stepwise logistic regression analysis model for the predictive value of IL-8

In the low IL-8 group has only a significant relationship with burn size (A). In patients with higher levels than the determined cut-off IL-8 levels there is a significant correlation with the incidence of sepsis (B). IL-8: confidence, cutoff, and prediction of sepsis (C).

Figure 5. Profile of major regulatory cytokines

Expression of IL-10, IL-12(p70), and IL-13 is associated with IL-8 expression (A, B, C).

Figure 6. Major regulatory mediators

Expression of G-CSF, IFN-gamma, MCP-1 (markers for granulocyte activation (A), inflammation (B), and macrophage activation (C) is higher in the group with high IL-8 levels.

Figure 7. Markers for Inflammation

Regulatory mediator (TNF-alpha), chemokine (MIP-1beta) and the established marker for inflammation CRP (C) in the high IL-8 group (A, B, C).

Figure 8. Organ specific markers

Elevation of organ specific markers for liver (A: bilirubin) and kidneys (B: Creatinine; C: BUN).