LEUKOTRIENE-B4 MARKEDLY ELEVATED IN THE EPITHELIAL LINING FLUID OF PATIENTS WITH CYSTIC-FIBROSIS

Persistent neutrophil infiltration into the airways of patients with c ystic fibrosis (CF) results in lung destruction. Eicosanoid lipid medi ators, particularly leukotriene B4 (LTB4), may play a role in neutroph il influx and activation. We compared the eicosanoid content of epithe lial lining fluid (ELF) obtained by bronchoalveolar lavage (BAL) from 17 patients with CF and 10 healthy subjects. LTB4 was the predominant eicosanoid in the CF airway (16.7 +/- 9.1 ng/ml ELF in CF versus 0.5 /- 0.1 ng/ml ELF in healthy subjects). Prostaglandins (PG) and thrombo xane (TX) were also elevated in CF (PGE2, 8.5 +/- 2.2; PGF2alpha, 6.0 +/- 2.0; and TXB2, 14.0 +/- 3.0 ng/ml ELF) compared with healthy subje cts (PGE2, 0.4 +/- 0.2; PGF2alpha, 0.5 +/- 0.2; and TXB2, 1.2 +/- 0.4 ng/ml ELF). We also developed a protocol for the storage and subsequen t analysis of BAL fluid that assures accurate and reproducible measure ments of these eicosanoids. BAL samples stored for up to 8 months reta in greater than 80% of their original eicosanoid content if the BAL fl uid is immediately treated with methanol, concentrated, and stored at -70-degrees-C without further purification. These data suggest that CF airways contain sufficient amounts of LTB4 both to recruit additional neutrophils into the airways and to stimulate neutrophils to release their injurious products. Therapies aimed at interfering with the prod uction or action of LTB4 may be beneficial in CF and other lung diseas es with a significant neutrophil response.