Neutrophil depletion attenuates interleukin-8 production in mild-overstretch ventilated normal rabbit lung

Mariko Kotani, Toru Kotani, Akitoshi Ishizaka, Seitaro Fujishima, Hidefumi Koh, Sadatomo Tasaka, Makoto Sawafuji, Eiji Ikeda, Kiyoshi Moriyama, Yoshifumi Kotake, Hiroshi Morisaki, Naoki Aikawa, Akira Ohashi, Kouji Matsushima, Yuh Chin T. Huang, Junzo Takeda

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)


Objective: Acute lung injury induced by lung overstretch is associated with neutrophil influx, but the pathogenic role of neutrophils in overstretch-induced lung injury remains unclear. Design: To assess the contribution of neutrophils, we compared the effects of noninjurious large tidal volume (VT) ventilation on lungs in normal and neutrophil-depleted animals. Setting: Research animal laboratory. Subjects: Twenty-six male Japanese white rabbits. Interventions: Animals were mechanically ventilated for 4 hrs with one of the three following protocols: large VT (20 mL/kg), small VT (8 mL/kg), and large VT (20 mL/kg) with neutrophil depletion achieved by a single dose of vinblastine injection (0.75 mg/kg) intravenously 4 days before the experiment. Measurements and Main Results: Large VT ventilation produced alveolar neutrophil influx compared with low VT (p = .002) without evidence of edema or increased epithelial permeability. The neutrophil influx was accompanied by increases in interleukin-8 in bronchoalveolar lavage fluid (p = .04). Immunohistochemistry of large VT lungs showed increased interieukin-8 staining in bronchial epithelial cells, alveolar epithelium, alveolar macrophages, and smooth muscles of pulmonary vessels. Neutrophil depletion attenuated the interleukin-8 increase in the lung. Large VT did not increase plasma interleukin-8 or tumor necrosis factor-α in plasma and bronchoalveolar lavage fluid. No expression of p-selectin or intercellular adhesion molecule-1 was observed. Conclusions: Cyclic overstretching of normal rabbit lungs with noninjurious large VT produced neutrophil influx and interleukin-8 increase in bronchoalveolar lavage fluid. Production of pulmonary interleukin-8 by lung overstretch might require the interaction between resident lung cells and migrated neutrophils. This study suggests that large VT ventilation potentiates the predisposed, subclinical lung injury, such as nosocomial pneumonia or aspiration of gastric contents.

Original languageEnglish
Pages (from-to)514-519
Number of pages6
JournalCritical care medicine
Issue number2
Publication statusPublished - 2004 Feb


  • Acute lung injury
  • Cell interaction
  • Interleukin-8
  • Mechanical ventilation
  • Neutrophil
  • Vinblastine

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine


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