TNF-ALPHA, IL-8, SOLUBLE ICAM-1, AND NEUTROPHILS IN SPUTUM OF CYSTIC-FIBROSIS PATIENTS

The cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-8 ( IL-8), and intercellular adhesion molecule-1 (ICAM-1) have important r oles in regulating neutrophil migration and the inflammatory response. To determine whether the concentration of these cytokines and soluble ICAM-1 (sICAM-1) in sputum was increased in patients with cystic fibr osis during acute exacerbations, we conducted (1) a cross-sectional st udy of 40 patients, 22 who were clinically well and 18 with acute pulm onary exacerbations; and (2) an 11 months longitudinal study of 16 pat ients. Significant differences in clinical scores, pulmonary function, and sputum neutrophil density were found between the acutely ill and the well group. There was a strong linear relationship (P < 0.0005) be tween TNF-alpha and IL-8 concentrations in sputum, but no association between clinical status and cytokine concentrations. The concentration of sICAM-1 was lower in acutely ill compared with well patients in th e cross-sectional study. Recovery of exogenous IL-8 added to sputum wa s complete, while recovery of TNF-alpha averaged 70%. Recovery of exog enous sICAM-1 was only 43%, and the recoveries were lower in sputum sa mples from acutely ill patients than those from stable patients (P = 0 .018). These data indicate that in cystic fibrosis patients, sputum co ncentrations of TNF-alpha and IL-8 are not increased during acute exac erbations of pulmonary inflammation. (C) 1996 Wiley-Liss, Inc.