Relation between Tumor Necrosis Factor-alpha and Granulocyte Elastase-α1-Proteinase Inhibitor Complexes in the Plasma of Patients with Cystic Fibrosis

Abstract

Patients with cystic fibrosis suffer from a chronic, progressively destructive bronchitis characterized by colonization of the airways by Pseudomonas aeruginosa. Cell wall lipopolysaccharides from P. aeruginosa may stimulate secretion of cytokines such as tumor necrosis factor alpha (TNF.alpha.) by monocytes/macrophages. We found elevated levels of TNF.alpha. (150 .+-. 60 pg/ml), interleukin-1.alpha. (144 .+-. 205 pg/ml), and interleukin-1.beta. (62 .+-. 100 pg/ml) in plasma from 25 patients with cystic fibrosis. In patients with less advanced disease, elevated plasma levels of TNF.alpha. correlated with high levels of complexes between neutrophil elastase and .alpha.1-proteinase inhibitor, suggesting that TNF.alpha. may be a mediator of neutrophil degranulation. TNF.alpha., by its chemotactic effect on neutrophils, may also contribute to the massive influx of neutrophils into and around the bronchial tree. Our findings raise the questions whether in patients with cystic fibrosis TNF.alpha. acts as cachectin and whether it mediates the anorexia that often results in weight loss.