Ventilator-induced heat shock protein 70 and cytokine mRNA expression in a model of lipopolysaccharide-induced lung inflammation

Intensive Care Med. 2003 Jun;29(6):915-922. doi: 10.1007/s00134-003-1747-6. Epub 2003 May 7.

Abstract

Objective: To investigate the effect of mechanical ventilation with no PEEP (ZEEP) and 4 cmH(2)O PEEP on heat shock protein 70 (HSP70) and pulmonary inflammatory cytokine expression in a model of lipopolysaccharide (LPS) induced lung inflammation.

Design and setting: Prospective, randomized, experimental animal study.

Subjects and interventions: We challenged 42 male Sprague-Dawley rats intratracheally with LPS. After 24 h the rats were randomly assigned to one of the ventilation strategies. Rats received either 4 h of mechanical ventilation with ZEEP or mechanical ventilation with 4 cmH(2)O PEEP. A nonventilated control group received LPS only. Lung pathology after LPS challenge was evaluated by histology to assess baseline lung injury. HSP70 and cytokine mRNA levels were measured in total lung homogenates.

Results: PaO(2) levels and lung histology revealed no deterioration after PEEP ventilation and severe deterioration after ZEEP ventilation. There was a significant higher expression of HSP70 and IL-1beta mRNA in the lungs of the ZEEP group than in the PEEP group and nonventilated controls. In the ZEEP group high HSP70 levels were correlated inversely with low IL-1beta mRNA and low IL-6 mRNA.

Conclusions: We propose that HSP70 expression protects the lung against ventilator-induced lung injury by decreasing cytokine transcription in the lung.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Disease Models, Animal*
  • HSP70 Heat-Shock Proteins / analysis*
  • HSP70 Heat-Shock Proteins / physiology
  • Immunohistochemistry
  • Inflammation
  • Interleukin-1 / analysis*
  • Interleukin-1 / genetics
  • Interleukin-6 / analysis*
  • Interleukin-6 / genetics
  • Leukocyte Count
  • Lipopolysaccharides / adverse effects*
  • Male
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Positive-Pressure Respiration / adverse effects*
  • Positive-Pressure Respiration / methods
  • Prospective Studies
  • Pulmonary Gas Exchange
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Respiration, Artificial / adverse effects
  • Respiration, Artificial / methods
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / immunology
  • Respiratory Distress Syndrome / metabolism
  • Respiratory Distress Syndrome / pathology*
  • Salmonella enteritidis*
  • Transcription, Genetic / physiology

Substances

  • HSP70 Heat-Shock Proteins
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • RNA, Messenger