ENDOTHELIN-1 EXCRETION IN URINE IN ACTIVE PULMONARY SARCOIDOSIS AND IN OTHER INTERSTITIAL LUNG-DISEASES

Endothelin-1 (ET-1) is a vasoactive, mitogenic peptide that is variabl y increased in Bronchoalveolar Lavage Fluid (BALF) and immunohistochem ically found in lung tissue of patients with Interstitial Lung Disease (ILD). To assess if endogenous ET-1 production is increased in ILD we evaluated 24 hour (24h) urine excretion of ET-1 in 20 patients with I LD and 10 healthy age-matched controls (HC). Eight patients with activ e pulmonary sarcoidosis (S), 6 with idiopathic pulmonary fibrosis (IPF ) and 6 with focal lung fibrosis due to inactive pulmonary tuberculosi s (hTB) were studied. Plasma ET-1 levels (ET-1pl, pg/ml) and 24h ET-1 levels in urine (ET-1ur, ng/24h) were measured by a specific radio-imm unoassay. Determinations of ET-1pl and ET-1ur were repeated in S and I PF patients after 30 days of prednisone (0.75 mg/kg/day) treatment. ET -1pl concentrations were not different between HC (5.34 +/- 0.48), S ( 5.95 +/- 0.96), IPF (4.75 +/- 1.37) and hTB (5.97 +/- 1.05) groups. ET -1ur was significantly higher in S (189.50 +/- 60.57) than in HC (69.0 0 +/- 10.76), IPF (62.17 -/+ 19.07) and hTB (82.00 +/- 24.97). After p rednisone, ET-1ur in the S group decreased significantly (189.50 +/- 6 0.57 to 94.00 +/- 13.60), and the decrease paralleled the improved cli nical status. In S patients, ET-1ur was not significantly correlated t o the degree of respiratory impairment, but it was significantly corre lated to the intensity of lymphocytic alveolitis (r=0.80). Patients wi th active S excrete higher amounts of ET-1 in the urine whereas patien ts with diffuse or focal pulmonary fibrosis do not, suggesting that ab normalities of ET-1 metabolism might be involved in the development an d/or progression of sarcoid granulomatous lung lesions. Urine ET-1 exc retion may be a potentially useful marker of disease activity in Sarco idosis patients.