Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury

Abstract Background and objectives Acute respiratory distress syndrome (ARDS) is a frequent form of hypoxiemic respiratory failure caused by the acute development of diffuse lung inflammation. Dysregulated systemic inflammation with persistent elevation of circulating inflammatory cytokines is the pathogenetic mechanism for pulmonary and extrapulmonary organ dysfunction in patients with ARDS. Glucocorticoids (GCs) have a broad range of inhibitory inflammatory effects, including inhibition of cytokines transcription, cellular activation and growth factor production. They inhibit the inflammatory pathways through two specific intracellular glucocorticoid receptors (GRs), named GR α and GR β . The aim of our study was to evaluate the histologic evidence of inflammatory injury and the GR α uptake of resident and inflammatory cells in different experimental models of acute lung injury (ALI). Methods We studied four groups of rats: three different experimental rat models of lung injury and a control group. The ALI was caused by barotrauma (due to an overventilation), oleic acid injection and mechanical ventilation. Results were compared to nonventilated rat control group. The duration of mechanical ventilation was of 2.5 h. At the end of each experiment, rats were sacrificed. Lung biopsies were evaluated for morphologic changes. The immunohistochemistry was performed to study GR α expression. Results Histologic evidence of lung injury (alveolar and interstitial edema, vascular congestion, alveolar haemorrhage, emphysema, number of interstitial cells and neutrophils, and destruction of alveolar attachments) were present in all ventilated groups. Barotrauma lead to an additional inflammatory response. GR α expression significantly increased in the three ventilated groups compared with nonventilated groups. GR α expression was highest in barotrauma group. Conclusions These data indicate that ALI is associated with diffuse alveolar damage, up-regulation of the inflammatory response and GR α overexpression. Barotrauma is the most effective mechanism inducing acute lung inflammation and GR α overexpression.