Parapneumonic Effusions Are Characterized by Elevated Levels of Neutrophil Extracellular Traps

Abstract

Neutrophil extracellular traps (NETs) increasingly are implicated in acute and chronic conditions involving multiple organ systems. Are NET concentrations higher in parapneumonic effusions compared with effusions of other origin and does this reflect the inflammatory nature of these effusions? Patients (N= 101) seeking hospital treatment for undifferentiated pleural effusion underwent pleural fluid classification based on cytologic analysis results, biochemical findings, microbiological characteristics, and clinical judgement. Concentrations of NET markers (extracellular DNA [eDNA], citrullinated histone H3 [citH3]), neutrophils (α-defensins), and inflammation (IL-1β)-related proteins were quantified by enzyme-linked immunosorbent assay. Differences between groups were analyzed using the Kruskal-Wallis one-way analysis of variance. Correlations used Spearman coefficient. Receiver operating characteristic (ROC) curves were calculated. Effusions were classified into four groups: parapneumonic (n= 18), malignant (n= 35), transudative (n= 22), and unclassifiable (n= 26). Concentrations of NETs markers were significantly higher in the parapneumonic group compared with malignant, transudative, and unclassifiable groups (median eDNA, 12.8ng/mL vs0.77ng/mL, 0.44ng/mL, and 0.86ng/mL [P< .001]; and median citH3, 127.1ng/mL vs0.44ng/mL, 0.34ng/mL, and 0.49ng/mL [P< .001]). citH3 and eDNA were correlated highly with lactate dehydrogenase (LDH; Spearman r= 0.66 and r= 0.73, respectively; P< .001) and moderately negatively correlated with pH (r= -0.55 and r= -0.62, respectively; P< .001). α-Defensins and IL-1β were higher in the parapneumonic group than in other groups (median α-defensins, 124.4ng/mL vs4.7ng/mL,7ng/mL, and 6.9ng/mL [P< .001]; and median IL-1β, 145 pg/mL vs1.87 pg/mL, 1.39 pg/mL, and 2.6 pg/mL [P< .001]) and moderately correlated with LDH (r= 0.60 and r= 0.57; P< .001). ROC curves showed high sensitivity and specificity for NET markers for prediction of parapneumonic effusion. High levels of some NET-related mediators in parapneumonic effusions correlate with inflammation. Effusions of other causes do not show high levels of NETs. These results may have treatment implications because NETs may be an important contributor to the inflammation and viscosity of parapneumonic effusions and may help us to understand the therapeutic benefit of deoxyribonuclease in empyema.