Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia

Intensive Care Med. 2004 Jan;30(1):68-74. doi: 10.1007/s00134-003-2060-0. Epub 2003 Nov 21.


Objective: To examine whether cytokine concentrations change in the pulmonary compartment during the development of ventilator-associated pneumonia (VAP).

Design: Non-directed bronchial lavage (NBL) was performed every 48 h in critically ill mechanically ventilated patients. Serial measurements of the cytokines tumor necrosis factor (TNF) alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-10 and the cytokine inhibitors soluble TNFalpha receptor type I (sTNFalphaRI), IL-1 receptor antagonist (IL-1Ra) and soluble IL-1 receptor II (sIL-1RII) were performed on the NBL fluid and matching plasma samples by ELISA.

Setting: An adult medical and surgical university hospital intensive care unit.

Patients: Nine patients who developed VAP and nineteen patients who did not develop VAP served as controls.

Interventions: None.

Results: Plasma concentrations of the measured cytokines and cytokine inhibitors did not change significantly in any patients. In control patients, NBL fluid concentrations of sIL-1RII decreased significantly over time (P=0.01). In patients who developed VAP, NBL fluid concentrations of TNFalpha, sTNFalphaRI, IL-1alpha, and IL-1beta increased significantly (P=0.002, P=0.03, P=0.04 and P=0.02, respectively). Furthermore, NBL fluid/plasma concentration ratios for TNFalpha, sTNFalphaRI, IL-1alpha, IL-1Ra and IL-6 increased significantly as VAP developed (P=0.001, P=0.001, P=0.04, P=0.03, and P=0.04, respectively).

Conclusion: Our results suggest that the production of important cytokines and cytokine inhibitors is compartmentalised within the lung in critically ill mechanically ventilated patients who develop VAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / analysis
  • Antigens, CD / blood
  • Body Fluid Compartments
  • Bronchoalveolar Lavage Fluid / cytology*
  • Case-Control Studies
  • Cytokines / analysis*
  • Cytokines / antagonists & inhibitors
  • Cytokines / blood*
  • Cytokines / immunology
  • England
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hospitals, University
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / analysis
  • Interleukin-1 / blood
  • Interleukin-10 / analysis
  • Interleukin-10 / blood
  • Interleukin-6 / analysis
  • Interleukin-6 / blood
  • Linear Models
  • Male
  • Middle Aged
  • Pneumonia, Bacterial / blood*
  • Pneumonia, Bacterial / etiology*
  • Pneumonia, Bacterial / immunology
  • Receptors, Interleukin-1 / analysis
  • Receptors, Interleukin-1 / blood
  • Receptors, Interleukin-1 Type I
  • Receptors, Tumor Necrosis Factor / analysis
  • Receptors, Tumor Necrosis Factor / blood
  • Receptors, Tumor Necrosis Factor, Type I
  • Respiration, Artificial / adverse effects*
  • Sialoglycoproteins / analysis
  • Sialoglycoproteins / blood
  • Time Factors
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism


  • Antigens, CD
  • Cytokines
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-6
  • Receptors, Interleukin-1
  • Receptors, Interleukin-1 Type I
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10