title: Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia.
abstract: OBJECTIVE
  To examine whether cytokine concentrations change in the pulmonary compartment during the development of ventilator-associated pneumonia (VAP).
  
  
  METHODS
  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.
  
  
  METHODS
  An adult medical and surgical university hospital intensive care unit.
  
  
  METHODS
  Nine patients who developed VAP and nineteen patients who did not develop VAP served as controls.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Intensive Care Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK, julian.millo@nda.ox.ac.uk
authors.forename: Julian L
authors.initials: JL
authors.lastname: Millo
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Conrad
authors.initials: C
authors.lastname: Williams
authors.forename: Gerrit J
authors.initials: GJ
authors.lastname: Weverling
authors.forename: Timothy
authors.initials: T
authors.lastname: Ringrose
authors.forename: Carolyn I
authors.initials: CI
authors.lastname: Mackinlay
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Garrard
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000097:blood; D001825:Body Fluid Compartments; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000097:blood* / Q000276:immunology; D004739:England; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006785:Hospitals, University; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis / Q000097:blood; D016753:Interleukin-10 / Q000032:analysis / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000097:blood* / Q000209:etiology* / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000097:blood; D053573:Receptors, Interleukin-1 Type I; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D012121:Respiration, Artificial / Q000009:adverse effects*; D012795:Sialoglycoproteins / Q000032:analysis / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10