ONO-5046 IS A POTENT INHIBITOR OF NEUTROPHIL ELASTASE IN HUMAN PLEURAL EFFUSION AFTER LOBECTOMY

The imbalance of neutrophil elastase and alpha(1)-antitrypsin in pleur al effusion after lobectomy and the effects of the neutrophil elastase inhibitors, sodium pionyloxy)phenyl-sulfonylamino]benzoyl]aminoacetic acid (ONO-5046) acid purified alpha(1)-antitrypsin, on neutrophil ela stase activity were determined. The amount of neutrophil elastase comp lexed to alpha(1)-antitrypsin, measured by an enzyme-linked immunosorb ent assay, was 170 times higher in pleural effusion than in blood 3 h after lobectomy. The alpha(1)-antitrypsin levels measured by laser nep helometry did not increase in either blood or pleural effusion. Althou gh neutrophil elastase activity, measured by the hydrolysis of succiny l-(Ala)(3)-p-nitroanilide, was not detected in blood, it was increased in pleural effusion 3 h and 24 h after lobectomy. ONO-5046, but not a lpha(1)-antitrypsin, reduced the neutrophil elastase activity in pleur al effusion. There is an imbalance of neutrophil elastase and alpha(1) -antitrypsin in pleural effusion after lobectomy. ONO-5046 is a potent inhibitor of neutrophil elastase activity in human pleural effusion. (C) 1998 Elsevier Science B.V. All rights reserved.