[Changes in plasma interleukin-33 concentration in sepsis and its correlation with seriousness of sepsis]

Abstract

Objective: To observe the changes in plasma interleukin-33 (IL-33) in patients with sepsis and its regularity, the association between IL-33 and the infection, and the significance of IL-33 in predicting the prognosis of sepsis.

Methods: A prospective single-center single-blind clinical study was conducted. Forty patients with sepsis in intensive care unit (ICU) of Shengjing Hospital of China Medical University from May 2012 to January 2013 were enrolled. The patients were divided into general sepsis, severe sepsis and septic shock groups according to the severity of systemic infection and presence of organ dysfunction. The sepsis patients were again divided into 28-day death group and survival group. Ten healthy volunteers and 11 patients with systemic inflammatory response syndrome (SIRS) were enrolled as healthy control and SIRS groups. The levels of procalcitonin (PCT), IL-33, IL-6, IL-1β, tumor necrosis factor-α (TNF-α), and IL-33 receptor sST2 were determined with enzyme linked immunosorbent assay (ELISA) within 3 hours, and 24 hours and 5 days after enrollment to ICU. The acute physiology and chronic health evaluation II (APACHE II) score was calculated. The clinical outcome, length of stay in ICU, and duration of mechanical ventilation were recorded. The relationship between IL-33 and each parameter was analyzed by Spearman analysis. Receiver operating characteristic (ROC) curve was drawn to evaluate IL-33 in predicting the outcome of sepsis.

Results: Plasma IL-33 in sepsis patients within 3 hours after admission was significantly increased compared with that of the healthy controls and SIRS group (ng/L: 15.43±7.22 vs. 0.67±0.24, 1.25±1.09, both P < 0.01). Compared with SIRS group, PCT in sepsis group was significantly increased [μg/L: 52.23 (19.69, 73.37) vs. 1.22 (0.69, 3.73), Z = -2.447, P < 0.001]. With exacerbation of illness, APACHE II score, the values of PCT and IL-33 were gradually increased in general sepsis, severe sepsis and septic shock groups, while the length of stay in ICU and the duration of mechanical ventilation were gradually prolonged (P < 0.05 or P < 0.01). The concentration of IL-33 (ng/L) of sepsis patients admitted to ICU within 3 hours, and 24 hours and 5 days of the illness was 15.43±7.22, 11.82±6.16, 5.55±2.25, respectively (F = 4.823, P = 0.004). There was a positive correction between IL-33 within 3 hours after ICU admission and APACHE II score (r = 0.351, P = 0.031), PCT (r = 0.412, P = 0.005), IL-6 (r = 0.535, P = 0.030), IL-1β (r = 0.674, P = 0.030), TNF-α (r = 0.250, P = 0.030), sST2 (r = 0.620, P < 0.001), and length of stay in ICU (r = 0.296, P = 0.013), duration of mechanical ventilation (r = 0.385, P = 0.011). Decreased plasma IL-33 level could be found in the survivors (n = 37, F = 7.798, P < 0.01), and its level in non-survivors (n = 3) was increased (F = 37.283, P > 0.05). The area under the ROC curve (AUC) of IL-33 and PCT in ROC curve were 0.821, 0.829. When the cut-off value of IL-33 was 13.79 ng/L, the sensitivity was 74.2%, the specificity was 79.6%; when the cut-off value of PCT was 4.70 μg/L, the sensitivity was 87.5%, and the specificity was 81.4%.

Conclusions: The concentration of IL-33 3 hours after ICU admission was obviously increased in sepsis patients, and it was positively correlated with PCT, therefore it is valuable in the diagnosis of the infection. In addition plasma IL-33 is related to the severity of sepsis. Its trend of change is valuable in predicting the outcome and in distinguishing sepsis from SIRS.