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Production of inflammatory cytokines in ventilator-induced lung injury: a reappraisal.

Authors
  • Ricard, J D1
  • Dreyfuss, D
  • Saumon, G
  • 1 Unité 82, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Xavier Bichat, Paris, France.
Type
Published Article
Journal
American journal of respiratory and critical care medicine
Publication Date
April 2001
Volume
163
Issue
5
Pages
1176–1180
Identifiers
PMID: 11316656
Source
Medline
License
Unknown

Abstract

We investigated the production of proinflammatory cytokines by the lung during high mechanical stretch in vivo. To do this, we subjected rats to high-volume (42 ml/kg tidal volume [VT]) ventilation for 2 h. The animals developed severe pulmonary edema and alveolar flooding, with a high protein concentration in bronchoalveolar lavage fluid (BALF). The animals' BALF contained no tumor necrosis factor (TNF)-alpha, negligible amounts of interleukin (IL)-1beta, and less than 300 pg/ml of the chemokine macrophage inflammatory protein (MIP)-2, an amount similar to that found in rats ventilated with 7 ml/kg VT. Systemic cytokine levels were below the detection threshold. Because isolated lungs have been shown to produce high levels of proinflammatory cytokines when ventilated with a similarly high VT for the same duration (Tremblay, et al. J Clin Invest 1997;99:944-952), we reconsidered this specific issue. We ventilated isolated, unperfused rat lungs for 2 h with 7 ml/kg or 42 ml/kg VT, or maintained them in a statically inflated state. Negligible amounts of TNF-alpha were found in the BALF whatever the ventilatory condition applied. The BALF IL-1beta concentration was slightly elevated and higher in lungs ventilated with 42 ml/kg VT than in those ventilated with 7 ml/kg VT or in statically inflated lungs (p < 0.05). The BALF MIP-2 concentration was moderately elevated in all isolated lungs (200 to 300 pg/ml), and was slightly higher (p < 0.05) in lungs ventilated with 42 ml/kg VT. After lipopolysaccharide (LPS) challenge, high levels of TNF-alpha, IL-1beta, and MIP-2 were found in the animals' plasma before the lungs were removed. Negligible amounts of TNF-alpha and IL-1beta were retrieved from the BALF of statically inflated lungs. The concentrations of TNF-alpha and IL-1beta were higher in the BALF of ventilated lungs (p < 0.001). The TNF-alpha level did not differ with the magnitude of VT, whereas the level of IL-1beta was significantly higher in BALF of lungs ventilated with 42 ml/kg VT (p < 0.01). The MIP-2 concentrations were similar for the two ventilatory conditions. These results suggest that ventilation that severely injures lungs does not lead to the release of significant amounts of TNF-alpha or IL-1beta by the lung in the absence of LPS challenge but may increase lung MIP-2 production.

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