The effect of secretory leukocyte proteinase inhibitor (SLPI) in a murine model of asthma

Abstract Rationale Serine Leukocyte Proteinase Inhibitor (SLPI) is a naturally occurring protease that protects the epithelial surface of the lung against several serine proteases. There is little data available on the effect of recombinant SLPI on the markers of inflammation and airway hyperresponsiveness (AHR). Hypothesis SLPI therapy will reduce inflammation and AHR in ovalbumin-sensitized C57/Black 6 mice. Objective To assess the effect of SLPI therapy on markers of inflammation and AHR. Methods C57/Black 6 mice were sensitized with ovalbumin (OVA) and divided into two groups and received 1) 30 μg recombinant SLPI 2) no treatment. Normal mice were also maintained as additional controls. SLPI was administered once weekly for three weeks, via nebulization to sensitized mice, three days after an OVA challenge was given. The mice were sacrificed 24 hours after SLPI was given, and measurements of eosinophil peroxidase activity (EPO), peripheral blood eosinophils (EOS), lung histology, serum IgE, and AHR to methacholine (Mch) challenge were performed. Control groups were also sacrificed at the same time points. Data were analyzed to compare sensitized untreated group with the normal or sensitized treated group using the student t test. Results SLPI therapy significantly decreased AHR to Mch challenge. There were no significant decreases in EPO, EOS, and serum IgE or lung inflammation on histopathological examination. Conclusions Our results show that recombinant SLPI therapy may decrease AHR in a murine model of asthma. The results from our study indicate that serine proteinases may play a role in AHR in asthma.