Effect of superoxide dismutase on a rabbit model of chronic allergic asthma.

Abstract

In bronchial asthma, inflammatory cells infiltrating the airway mucosa release oxygen radicals that cause tissue damage and amplify the airway inflammation. Antioxidant enzymes may have a protective effect on the airways. The purpose of this study was to determine whether treatment of a rabbit model of chronic allergic asthma with the antioxidant enzyme superoxide dismutase conjugated to polyethylene glycol will protect the airways from oxygen radical injury, decrease airway inflammation, and attenuate the asthmatic response. New Zealand white rabbits were sensitized to ragweed. Baseline histamine PC30, ragweed PD30, and early and late phase asthmatic response to ragweed bronchial challenge were measured. The rabbits were then randomized into two groups that received every 48 hours an intravenous dose of either superoxide dismutase-polyethylene glycol 10,000 U/kg or inactivated superoxide dismutase-polyethylene glycol as control, followed by a 1-hour exposure to aerosolized ragweed extract. After 4 weeks the rabbits had a second bronchial challenge, were sacrificed, and lung histology was studied. On the posttreatment challenge, the superoxide dismutase-polyethylene glycol group had a rise in ragweed PD30, while the control group had no change in ragweed PD30, and two of five rabbits in the superoxide dismutase-polyethylene glycol group did not have an early or late phase asthmatic response, while all rabbits in the control group had an asthmatic response. There was no significant difference in lung histology between both groups. A rabbit model of chronic allergic asthma treated with superoxide dismutase-polyethylene glycol showed a trend of improvement in airway responsiveness but no significant effect on airway inflammation.