Expression of glucocorticoid receptors a and b in steroid sensitive and steroid insensitive interstitial lung diseases

Background: Sensitivity to glucocorticoids may be related to the concentration of glucocorticoid receptors a (GRa) and b (GRb). A study was undertaken to assess GRa and GRb expression in steroid insensitive interstitial lung disease (idiopathic pulmonary fibrosis (IPF)) and steroid sensitive interstitial lung diseases (sarcoidosis and cryptogenic organising pneumonia (COP)). Methods: Lung tissue was obtained from control subjects and from patients with IPF, sarcoidosis, and COP. Pulmonary function tests were carried out at the time of lung biopsy and every 3 months. GRa and GRb expression was evaluated by both competitive RT-PCR and immunohistochemistry. Data are presented as median and 25–75th percentile. Results: GRa mRNA expression (10 cDNA copies/mg total RNA) was higher in patients with steroid sensitive interstitial lung diseases (10.0; 7.8–14.9; n = 11) than in patients with IPF (4.4; 3.2–6.6; n = 19; p,0.001). GRb expression was at least 1000 times lower than that of GRa and did not differ between the three groups. A negative correlation was found between GRa mRNA levels and the fibrotic pathology score of the tissue (r=20.484, p,0.01) and a positive correlation was found between GRa mRNA levels and improvement in forced vital capacity (r = 0.633; p,0.01) after treatment of patients with glucocorticoids. Immunoreactivity for GR protein was also higher in patients with sarcoidosis and COP than in those with IPF. Conclusion: The variable response of some interstitial lung diseases to steroid treatment may be the result of differences in the expression of GRa.