The Effect of Daily Apolipoprotein A-I Mimetic Therapy on T15-Type Autoantibodies Against Oxidized Phosphatidylcholine in a Murine Model of Asthma

Abstract

RATIONALE: Phospholipid derived proinflammatory lipids have been shown to regulate mononuclear and vascular cell dysfunction in vascular disease. T15-type antibodies bind proinflammatory lipids such as oxidized phosphatidylcholine (ox-PC) and therefore may be utilized as a marker of inflammation. The apolipoprotein (apo) A-I mimetic, D-4F has been shown to bind and remove pro-inflammatory lipids and therefore may play a pivotal role in decreasing pulmonary inflammation similar to what occurs in asthma. METHODS: C57/Black 6 mice were sensitized with ovalbumin, divided into two groups and received: (1) intranasal D-4F (20 μg) once a day for 4 weeks or (2) no treatment for 4 weeks. Normal mice were also maintained as additional controls. At the time of sacrifice samples were collected for eosinophil peroxidase activity (EPO) in the bronchioalveolar lavage fluid (BAL), lung histology, and serum IgE levels. Data were analyzed to compare sensitized D-4F treated group with the sensitized untreated and normal, untreated unsensitized groups using student t test. RESULTS: D-4F therapy resulted in decreases in ox-PC, EPO, serum IgE levels, and inflammation on lung histology. The therapy was tolerated without evidence of toxicity. CONCLUSIONS: D-4F therapy resulted in a significant decrease in lung inflammation, serum IgE levels and EPO in experimental asthma. This study also demonstrates efficacy of D-4F to decrease proinflammatory phospholipids in the lung in a murine model of asthma. This novel drug may provide a safe and effective alternative to currently available therapies in treating asthma.