STLR-2 levels can discriminate between infective and non-infective origins of multi-organ dysfunction on ICU admission: a pilot study

Introduction: Toll like receptors are pattern recognition receptors activated by microbial binding which lead to the ‘switching on’ of downstream pro-inflammatory genes and inflammatory mediator secretion. Soluble toll like receptor 2 (sTLR-2) was discovered as a naturally occurring ‘decoy’ receptor, blocking the interaction between TLR-2 and its accessory molecule, thus attenuating the response to insult. Hypothesis: We hypothesise that (1) sTLR-2 expression in septic patients will differ from SIRS (systemic inflammatory response) patients who have not suffered an infective insult; and (2) the plasma sTLR-2 concentration will correlate with clinical outcome. Methods: A cohort of intensive care patients admitted with sepsis (N=36), or SIRS (N=10) were recruited to the study. Blood samples were taken and plasma extracted on admission then daily, up to day 7. An Elisa (RnD systems) was used to quantify sTLR-2 expression. P values were obtained using a Mann Whitney U-test, with P Results: There was a significant difference in sTLR-2 expression between those patients diagnosed with sepsis and SIRS on admission, p= 0.001. A cut off value of 0.9ng/ml provided a sensitivity of 77.78% and a specificity of 100% when using sTLR-2 as a biomarker of infection in patients admitted to ICU with organ failure, giving an AUC of 0.837. PPV 100%, NPV 55.56%. In the SIRS group, high levels of sTLR-2 were associated with mortality. On the other hand, in the sepsis group low sTLR-2 levels predicted a worse outcome. Conclusions: In our pilot study we have shown for the first time that quantifying sTLR-2 expression in septic and SIRS patients on admission to ICU is a reliable ‘rule in’ biomarker of the patient’s infective status. This provides a convenient method of determining the presence of infection for correct antibiotic administration. sTLR-2 expression also indicates clinical outcome where interestingly, low levels appear detrimental to sepsis patients and of benefit in SIRS. Although further studies are required, sTLR-2 shows great promise as a biomarker of infection and potential prognostic marker.