Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia.
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.
Millo
Julian L
JL
Intensive Care Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK, julian.millo@nda.ox.ac.uk
Schultz
Marcus J
MJ
Williams
Conrad
C
Weverling
Gerrit J
GJ
Ringrose
Timothy
T
Mackinlay
Carolyn I
CI
van der Poll
Tom
T
Garrard
Christopher S
CS
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
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