NEUTROPHIL ELASTASE ALPHA(1)-PROTEINASE INHIBITOR COMPLEX LEVELS DECREASE IN PLASMA OF CYSTIC-FIBROSIS PATIENTS DURING LONG-TERM ORAL BETA-CAROTENE SUPPLEMENTATION

Lung inflammation in cystic fibrosis (CF) is associated with an increa sed release from activated neutrophils of oxidants and proteinases. Fr ee radical generation is not efficiently neutralized, and the major an ti-proteinase, alpha(1)-proteinase inhibitor (alpha(1)-PI) is thought to be oxidatively inactivated. We hypothesized that enhanced antioxida nt protection could represent an additional long-term strategy to atte ntuate the host inflammatory response. The effect on plasma neutrophil elastase/alpha(1)-PI (NE/alpha(1)-PI) complex levels (as a marker of lung inflammation) and plasma malondialdehyde concentrations (as a mar ker of lipid peroxidation) of additional oral beta-carotene supplement ation was studied in 33 CF patients who had already received long-term vitamin E supplementation. In the presence of a more than 10-fold inc rease in plasma beta-carotene concentrations (mean +/- SEM) (0.09 +/- 0.01 to 1.07 +/- 0.19 mu mol/L; p < 0.0001), a small increase in plasm a alpha-tocopherol concentrations (23.8 +/- 1.31 to 28.4 +/- 1.81 mu m ol/L; p = 0.02), and a more than 50% decrease in plasma malondialdehyd e concentrations (1.00 +/- 0.07 to 0.46 +/- 0.03 mu mol/L; p < 0.0001) , plasma NE/alpha(1)-PI complex levels decreased from 102.2 +/- 16.0 t o 83.0 +/- 10.4 mu g/L; (p = 0.02). Plasma retinol concentrations incr eased (1.05 +/- 0.06 to 1.23 +/- 0.07 mu mol/L; p = 0.0001) due to con version of beta-carotene to retinol, which could have contributed to t he decrease in NE/alpha(1)-PI complex levels. Based on these results, we speculate that efficient antioxidant supplementation could attenuat e lung inflammation in CF.