Injurious ventilation induces widespread pulmonary epithelial expression of tumor necrosis factor-alpha and interleukin-6 messenger RNA

Crit Care Med. 2002 Aug;30(8):1693-700. doi: 10.1097/00003246-200208000-00003.


Objective: We examined the hypothesis that injurious strategies of mechanical ventilation alter the expression and distribution within the lung of tumor necrosis factor-alpha and interleukin-6 that are both duration and ventilation strategy dependent.

Subjects: Male Sprague Dawley rats.

Interventions: Lungs from rats were preserved immediately after death or were randomized to ex vivo ventilation with either a) noninjurious ventilation; b) high end-inspiratory lung volume with positive end-expiratory pressure (PEEP); c) high end-inspiratory lung volume without PEEP; or d) intermediate lung distension without PEEP, for periods ranging from 30 mins to 3 hrs.

Measurement and main results: Changes in cytokines were assessed by in situ hybridization, immunocytochemistry, simultaneous in situ hybridization and immunocytochemistry, Northern analysis, and enzyme-linked immunosorbent assay. Whereas minimal expression of tumor necrosis factor-alpha and interleukin-6 mRNA was found in lungs subjected to noninjurious ventilation, the three injurious strategies resulted in a diffuse increase in expression of tumor necrosis factor-alpha and interleukin-6. The principal cells involved were the bronchial, bronchiolar, and alveolar epithelium. The changes in tumor necrosis factor-alpha mRNA and protein expression were dependent on both duration of ventilation and the ventilation strategy used.

Conclusions: The vast pulmonary epithelium is a major contributor to ventilation-induced changes in cytokine production and may play an important role in the pathogenesis of lung injury and systemic sequelae in ventilated subjects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Bronchoalveolar Lavage Fluid / chemistry
  • Disease Models, Animal
  • In Situ Hybridization
  • Interleukin-6 / genetics*
  • Lung / blood supply*
  • Lung / metabolism*
  • Lung Compliance / physiology
  • Male
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Respiration, Artificial / adverse effects*
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / physiopathology*
  • Treatment Failure
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Biomarkers
  • Interleukin-6
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha