Ventilator-induced lung injury leads to loss of alveolar and systemic compartmentalization of tumor necrosis factor-alpha

Intensive Care Med. 2000 Oct;26(10):1515-22. doi: 10.1007/s001340000648.


Objectives: To determine the effect on compartmentalization of the tumor necrosis factor (TNF)-alpha response in the lung and systemically after ventilation with high peak inspiratory pressure with and without positive end-expiratory pressure (PEEP).

Design and setting: Prospective, randomized, animal study in an experimental laboratory of a university.

Subjects and interventions: 85 male Sprague-Dawley rats. Lipopolysaccharide was given intratracheally or intraperitoneally to stimulate TNF-alpha production; control animals received a similar amount of saline. Animals were subsequently ventilated for 20 min in a pressure control mode with peak inspiratory pressure/PEEP ratio of either 45/0 or 45/10 (frequency 30 bpm, I/E ratio 1:2, FIO2 = 1).

Measurements and results: Blood gas tension and arterial pressures were recorded at 1, 10, and 20 min after start of mechanical ventilation. After killing of the animals pressure-volume curves were recorded, and bronchoalveolar lavage (BAL) was performed for assessment of protein content and the small/large surfactant aggregate ratio. TNF-alpha was determined in serum and BAL. TNF-alpha levels were significantly increased after lipopolysaccharide stimulation; furthermore ventilation without PEEP resulted in a significant shift of TNF-alpha to the nonstimulated compartment as opposed to ventilation with a PEEP level of 10 cmH2O.

Conclusions: Ventilation strategies which are known to induce ventilation-induced lung injury (VILI) disturb the compartmentalization of the early cytokines response in the lung and systemically. Furthermore, the loss of compartmentalization is a two-way disturbance, with cytokines shifting from the vascular side to the alveolar side and vice versa. A ventilation strategy (PEEP level of 10 cmH2O) which prevents VILI significantly diminished this shift in cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood Gas Analysis
  • Blood Pressure
  • Bronchoalveolar Lavage Fluid / chemistry
  • Disease Models, Animal*
  • Inflammation
  • Lipopolysaccharides
  • Male
  • Positive-Pressure Respiration / adverse effects*
  • Positive-Pressure Respiration / methods
  • Prospective Studies
  • Pulmonary Alveoli / chemistry*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / etiology*
  • Respiratory Distress Syndrome / metabolism*
  • Respiratory Distress Syndrome / physiopathology
  • Tidal Volume
  • Time Factors
  • Tumor Necrosis Factor-alpha / analysis*
  • Tumor Necrosis Factor-alpha / metabolism*


  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha