Significance of increase in lipocortin-1 gene transcripts in the blood monocytes of patients with pulmonary sarcoidosis.

BACKGROUND AND AIM OF THE WORK: Lipocortin-1 (also known as annexin-1) is upregulated by corticosteroids and plays a prominent part in many of their anti-inflammatory actions. In our previou investigation, lipocortin-1 gene expression in blood monocytes was higher in sarcoidosis patients tha in healthy subjects or IPF patients. In this study, we examined the amounts of lipocortin-1 gene tran scripts [at baseline and after stimulation by synthetic adrenocorticotrophic hormone (ACTH)] in the blood monocytes of sarcoidosis patients, and then we analyzed the relationships between these amount and several clinical indexes. METHODS: Serum and blood monocyte samples were prepared from 21 sar coidosis patients before and after ACTH stimulation. The amounts of lipocortin-1 and beta-actin gene tran scripts obtained from monocytes were quantified by RT-PCR. The patients were prospectively followe for at least 2.5 years. RESULTS: 1. Serum cortisol was increased in all patients after synthetic ACTH in jection. 2. Lipocortin-1 gene transcripts tended to increase in parallel with increases in serum cortisol but the relationship was not significant. 3. The amounts of lipocortin-1 gene transcripts induced by syn thetic ACTH were related to two indexes of disease activity/extension: the presence of parenchymal lesions (p = 0.018), and the presence of extrathoracic lesions (p = 0.043). 4. After 3 years of follow-up the patients with higher basal amounts of lipocortin-1 gene transcripts in monocytes showed improve ment of sACE activity and FEV1/FVC%. CONCLUSION: The amounts of lipocortin-1 gene transcripts induced by synthetic ACTH were related to the presence of parenchymal lesions, while their basa amounts correlated with either improvement of sACE activity or stabilization of FEV1/FVC%.