INDUCTION OF BIOLOGICALLY-ACTIVE INTERLEUKIN-8 FROM LUNG EPITHELIAL-CELLS BY BURKHOLDERIA (PSEUDOMONAS) CEPACIA PRODUCTS

The frequency of isolation of Burkholderia cepacia from the sputum of cystic fibrosis (CF) patients is increasing, Using the human A549 lung epithelial cell line, we have investigated the ability of B. cepacia exoproducts to stimulate interleukin-8 (IL-8) release, Cell-free super natants from a panel of CF clinical, non-CF clinical, and nonclinical B. cepacia isolates were found to stimulate IL-8 release, with levels ranging from 11.8 +/- 2.8 to 80.0 +/- 3.5 ng/ml, A similar pattern was seen at the level of the IL-8 mRNA, The bioactivity of the IL-8 was c onfirmed by examining its effect on the intracellular free calcium in neutrophils and inhibition by a neutralizing anti-IL-8 antibody, B. ce pacia lipopolysaccharide, which was able to stimulate IL-8 release fro m monocytes, did not release IL-8 from the A549 cells, Furthermore, th e stimulating ability of the bacterial cell-free supernatant was not d iminished by polymyxin B, was markedly reduced by boiling, and appeare d unrelated to N-acylhomoserine lactones. The ability of B. cepacia to elicit IL-8 release from epithelial cells may be important in the pat hology of CF.