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


METHODS
Prospective, randomized, experimental animal study.


METHODS
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.
Pediatric Intensive Care Unit, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands.|Laboratory for Psychoneuroimmunology, Department of Immunology, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
Harriët A
HA
Vreugdenhil
Department of Anesthesiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Jack J
JJ
Haitsma
Pediatric Intensive Care Unit, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands.
Koos J
KJ
Jansen
Laboratory for Psychoneuroimmunology, Department of Immunology, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
Jitske
J
Zijlstra
Department of Pediatrics, VU Medical Center, Amsterdam, The Netherlands.
Frans B
FB
Plötz
Department of Veterinary Pathology, University of Utrecht, Utrecht, The Netherlands.
Jaap E
JE
van Dijk
Department of Anesthesiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Burkhard
B
Lachmann
Pediatric Intensive Care Unit, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands.
Hans
H
van Vught
Laboratory for Psychoneuroimmunology, Department of Immunology, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
Cobi J
CJ
Heijnen
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis* / Q000502:physiology; D007150:Immunohistochemistry; D007249:Inflammation; D007375:Interleukin-1 / Q000032:analysis* / Q000235:genetics; D015850:Interleukin-6 / Q000032:analysis* / Q000235:genetics; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011175:Positive-Pressure Respiration / Q000009:adverse effects* / Q000379:methods; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects / Q000379:methods; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012477:Salmonella enteritidis; D014158:Transcription, Genetic / Q000502:physiology
D018840:HSP70 Heat-Shock Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger