Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection

Front Immunol. 2019 Aug 2:10:1798. doi: 10.3389/fimmu.2019.01798. eCollection 2019.

Abstract

Background: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and β-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection.

Keywords: hematologic malignancy; interleukin-6; interleukin-8; invasive mold infection; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism*
  • Bronchoalveolar Lavage Fluid
  • Bronchoscopy / methods
  • Female
  • Fungi / metabolism*
  • Galactose / analogs & derivatives
  • Hematologic Neoplasms / metabolism*
  • Humans
  • Interleukin-6 / metabolism*
  • Interleukin-8 / metabolism*
  • Male
  • Mannans / metabolism
  • Middle Aged
  • Prospective Studies
  • ROC Curve
  • Respiratory Tract Infections / metabolism*

Substances

  • Biomarkers
  • CXCL8 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • Mannans
  • galactomannan
  • Galactose