Secretory leukocyte protease inhibitor (SLPI) is a potent
proteinase inhibitor produced in the lung. Stimulated neutrophils at sites of
inflammation can inactivate SLPI by
myeloperoxidase-mediated oxidation of the
methionine residue in the active site of SLPI.
Apocynin is a selective inhibitor of
NADPH oxidase and may therefore protect SLPI against neutrophil-mediated oxidative inactivation. The aim of the present study was to determine the effect of
apocynin on the efficacy of SLPI in preventing experimental
emphysema. To investigate the effect of
apocynin on
emphysema without SLPI treatment, three groups of eight hamsters each received
drinking water containing
apocynin at concentrations of 2, 20, and 200 micrograms/ml, respectively.
Emphysema was induced in these hamsters by intratracheal instillations of 500 micrograms of
lipopolysaccharide (LPS) twice a week for 4 wk. In hamsters that received 200 micrograms/ml
apocynin, the development of
emphysema was reduced by 26.2% (p = 0.01). Other
apocynin concentrations had no effect. The experiment was repeated, with SLPI added to the treatment. Of a total of six groups of hamsters, four groups (three with
apocynin and one with
solvent) received twice-weekly doses of a mixture of 500 micrograms of LPS and 1 mg SLPI in 200 microliters saline in the trachea for 4 wk. In addition, each LPS instillation was followed 24 and 48 h later by an instillation containing 1 mg of SLPI.
Apocynin (20 and 200 micrograms/ml) improved the protective effect of SLPI from 37 to 64% and 79%, respectively (p < 0.01). We conclude that
oral administration of
apocynin can improve the efficacy of SLPI in preventing LPS-induced
emphysema.