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. 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-1β 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-1β 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.