The role of resistin and myeloperoxidase in severe sepsis and septic shock: Results from the ALBIOS trial

Background Inflammatory biomarkers are useful in detecting patients with sepsis. The prognostic role of resistin and myeloperoxidase (MPO) has been investigated in sepsis. Materials and Methods Plasma resistin and MPO were measured on days 1, 2 and 7 in 957 patients enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. The association between resistin and MPO levels on day 1, 2 and 7 and 90‐day mortality was assessed. Results Plasma resistin and MPO concentrations were higher at day 1 and decreased until day 7. Both biomarkers were positively correlated with each other and with physiological parameters. Higher levels of resistin and MPO on day 1 were associated with the development of new organ failures. Patients experiencing death at 90 days showed higher levels of resistin and MPO compared with survivors. At day 1, only MPO in the 4th quartile (Q4), but not resistin, was found to predict 90‐day death (adjusted hazard ratio [aHR] 1.55 vs Q1). At day 2, resistin in the Q3 and Q4 predicted a > 40% increase in mortality as also did MPO in the Q4. On day 7, Q4 resistin was able to predict 90‐day mortality, while all quartiles of MPO were not. Conclusions High levels of MPO, but not of resistin, on day 1 were able to predict 90‐day mortality. These findings may either suggest that early hyper‐activation of neutrophils is detrimental in patients with sepsis or reflect the burden of the inflammatory process caused by sepsis. Further studies are warranted to deepen these aspects (ALBIOS ClinicalTrials.gov Identifier: NCT00707122). Infectious stimuli (bacteria, viruses or fungi) stimulate the response of the immune system. In recent years, a wealth of biomarkers have been studied. Resistin is a cytokine mainly produced by macrophages, but also by adipocytes and neutrophils. After being released, resistin directly binds the CAP1 receptor on monocytes and adipocytes and upregulates the transcription of inflammatory cytokines. However, resistin can also impair neutrophil functions by reducing chemotaxis and oxidative burst, two important functions through which neutrophils cope with invading pathogens. In pre‐clinical studies, resistin has been described to bind TLR4 and increase CCL4 expression, causing macrophage infiltration. In human studies, however, no evidence of direct binding between TLR4 and human resistin has been found and this mechanism can be only hypothesized at the moment. On the other side, MPO is the most abundant product of neutrophil degr