Effect of mechanical ventilation on cytokine response to intratracheal lipopolysaccharide.
BACKGROUND
Mechanical ventilation may cause lung injury through the excitation of an inflammatory response and the release of mediators, such as cytokines. The authors tested the hypothesis that intratracheal lipopolysaccharide amplifies the cytokine response to mechanical ventilation.


METHODS
Rat lungs were intratracheally instilled with lipopolysaccharide followed by ex vivo mechanical ventilation for 2 h with low tidal volume of 7 ml/kg with 3 cm H2O positive end-expiratory pressure (PEEP), high tidal volume of 40 ml/kg with zero PEEP, medium tidal volume of 15 ml/kg with 3 cm H2O PEEP, or medium tidal volume and zero PEEP.


RESULTS
In the absence of lipopolysaccharide, lung lavage concentrations of tumor necrosis factor and interleukin 1 beta but not macrophage inflammatory protein 2 were significantly higher in lungs ventilated at high tidal volume/zero PEEP than at low tidal volume. There was a marked increase in lavage tumor necrosis factor and macrophage inflammatory protein 2 concentrations in lungs ventilated at low tidal volume after exposure to intratracheal lipopolysaccharide at doses of 100 ng/ml or greater. However, in lungs ventilated at high tidal volume, this response to lipopolysaccharide was markedly reduced. In addition, the number of alveolar macrophages recovered in the lavage was significantly lower in lungs ventilated at high tidal volume.


CONCLUSIONS
Ventilation strategy can modify lung cytokine responses to lipopolysaccharide, likely through an effect on the alveolar macrophage population.
Whitehead
Thomas C
TC
Departments of Anesthesia and Critical Care Medicine, St Michael's Hospital, University of Toronto, Canada.
Zhang
Haibo
H
Mullen
Brendan
B
Slutsky
Arthur S
AS
D000280:Administration, Inhalation; D000399:Air Pressure; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002454:Cell Differentiation; D054426:Chemokine CXCL2; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D007442:Intubation, Intratracheal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000502:physiology; D008297:Male; D015846:Monokines / Q000378:metabolism; D051381:Rats; D012121:Respiration, Artificial / Q000009:adverse effects*; D012129:Respiratory Function Tests; D013990:Tidal Volume / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054426:Chemokine CXCL2; D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha