Role of interleukin-3 as a prognostic marker in septic patients

Abstract

ObjectiveTo evaluate the accuracy of IL-3 to predict the outcome of septic patients.MethodsProspective cohort study with adult patients in an intensive care unit with sepsis or septic shock diagnosed within the previous 48 hours. Circulating IL-3 levels were measured upon inclusion (day 1) and on days 3 and 7. The primary outcome was hospital mortality.ResultsOne hundred and twenty patients were included. Serum levels of IL-3 on day 1 were significantly higher among patients who died than among patients who survived the hospital stay (91.2pg/mL versus 36pg/mL, p = 0.024). In a Cox survival model considering the IL-3 levels at inclusion, age and sequential SOFA, IL-3 values remained independently associated with mortality (HR 1.032; 95%CI 1.010 - 1.055; p = 0.005). An receiver operating characteristic curve was built to further investigate the accuracy of IL-3, with an area under the curve of 0.62 (95%CI 0.51 - 0.73; p = 0.024) for hospital mortality. A cutoff initial IL-3 value above 127.5pg/mL was associated with hospital mortality (OR 2.97; 95%CI: 1.27 - 6.97; p = 0.0019) but with a low performance (82% for specificity, 39% for sensibility, 53% for the positive predictive value, 72% for the negative predictive value, 0.73 for the negative likelihood and 2.16 for the positive likelihood ratio).ConclusionHigher levels of IL-3 are shown to be independently associated with hospital mortality in septic patients but with poor clinical performance.

Two new immature and dysfunctional neutrophil cell subsets define a predictive signature of sepsis useable in clinical practice

“…Moreover, the authors described an association between high plasma IL-3 levels and high mortality. This result was also obtained in a recent prospective cohort study, where higher levels of IL-3 were shown to be independently associated with hospital mortality in septic patients (17). All these results identify IL-3 and its receptor CD123 as an orchestrator of emergency myelopoiesis, and reveals a new target for the diagnosis and treatment of sepsis.…”

“…High level of neutrophil CD64, measured in the peripheral blood, could also be due to released immature granulocytes from the bone marrow, especially when CD64 expression is associated with decreased expression of neutral endopeptidase (CD10) and lowaffinity immuno-globulin-Fc fragment III (CD16) (9, 10, 14) (Supplemental Table1) (15). Previous studies identified also the interleukin (IL)-3 as an orchestrator of emergency myelopoiesis during sepsis, and showed its association with hospital mortality (17,18). In parallel, programmed death ligand-1 (PD-L1) expressed on monocytes was also described as a mortality-predictor in sepsis patients (18,19).…”

Two New Neutrophil Subsets Define a Discriminating Sepsis Signature

“…CD64 is normally expressed on monocytes, but its expression on circulating neutrophils could be due to its upregulation during inflammation (17), or to released immature granulocytes from the bone marrow, especially when it is associated with decreased expression of neutral endopeptidase (CD10) and low-affinity immuno-globulin-Fc fragment III (CD16) (13,14,18) (Supp.Tab.1) (19). Previous studies identified also the interleukin (IL)-3 as an orchestrator of emergency myelopoiesis during sepsis and showed its association with hospital mortality (20,21). In parallel, programmed death ligand-1 (PD-L1) expressed on monocytes was also described as a mortalitypredictor in sepsis patients (22,23).…”

Biomarkers of Infection and Inflammation

“…55,56 Many of the inflammation-promoting cytokines (e.g., interleukin-3, interleukin-6, interleukin-8, interleukin-27, interleukin-37) are being studied as possible biomarkers for bacterial infections, specifically sepsis. [57][58][59][60][61] Additionally, innate immune system cells, such as neutrophils and monocytes, are being further evaluated as promising biomarkers that would be used in conjunction with more traditional biomarkers. 62,63 In comparison to traditional biomarkers, the use of biomarkers in sepsis is in its infancy and more research is required.…”