Time course of IL-6 and LBP, candidate biomarkers of sepsis in surgical critical care

Introduction

The outcome of sepsis in critically ill patients relies on rapid identification and therapy. However, identification of sepsis in these patients is challenging, and focus has shifted towards biological surrogates as diagnostic/therapeutic biomarkers. IL-6 and lipopolysaccharide binding protein (LBP) may have such a potential.

Methods

Retrospective analysis of daily IL-6 and LBP serum levels over the course of a 3-month laboratory feasibility study of large-scale chemiluminescent immunometric assays on unused residuals of routine patient blood samples from the surgical critical care unit. We determined the time course of IL-6 and LBP over septic events defined as 4 days before and after the initiation of antimicrobial therapy as day 0 (n = 40). Variations over time of IL-6 and LBP in both absolute values and amplitude were measured between day -4 to day 0 and day 0 to day +4. Candidate biomarker variations were assessed for coherence with clinical evolution of sepsis to determine biomarker-like behavior.

Results

Only amplitudes of variation were coherent with clinical evolution of sepsis rather than variations in absolute values or values relative to published thresholds. Coherence between patient evolution and biomarker time course was 93% for IL-6 and 85% for LBP. IL-6 levels always increased to over at least 50% of baseline (51 to 2,523%) before initiation of antibiotics. IL-6 decreased by at least 45% (45 to 98%) of the maximal value when sepsis resolved successfully with antimicrobial therapy in 92% of the cases. Stagnating IL-6 levels always paralleled absence of resolution of sepsis. No pre-antimicrobial initiation increase of LBP was observed. LBP always decreased by at least 16% (16 to 85%) of the maximal value when sepsis resolved successfully with antimicrobial therapy. LBP increase after initiation of antimicrobials or LBP stagnation paralleled absence of clinical resolution. Concordant patterns of both IL-6 and LBP were always coherent with clinical evolution but only concerned 35% of the cases.

Conclusions

IL-6 and LBP behave as biomarkers over the course of sepsis in surgical critical care patients. Only dynamic monitoring may yield any information relevant to diagnosis or treatment follow-up. It remains to be shown how well these biomarkers perform through other study designs.