Effects of omalizumab and budesonide on markers of inflammation in human bronchial epithelial cells

Abstract

Many patients with asthma have an IgE-mediated allergic component to the disease. Omalizumab, a monoclonal anti-IgE antibody, has demonstrated clinical efficacy in patients with allergic asthma. The effects of omalizumab on inflammation in asthma are not completely understood. To evaluate the effects of omalizumab on allergen- and growth factor-stimulated proinflammatory cytokine and nitric oxide (NO) production in human bronchial epithelial cells (BECs) and to compare them to the effects of budesonide, a corticosteroid with known anti-inflammatory properties. Human BECs were stimulated in duplicate with interleukin 1beta (IL-1beta), 100 U/mL; ragweed, 10 microg/mL; dust mite, 1000 AU; and epithelial growth factor, 40 ng/mL; and either 10(-7) M budesonide or 0.1 microg/mL of omalizumab in a 4% dust mite atopic serum medium for 6 and 24 hours in 5% carbon dioxide at 37 degrees C. Tumor necrosis factor alpha and transforming growth factor betaexpression and production and IL-4, IL-13, and NO production were assayed using gene-specific messenger RNA or sensitive enzyme-linked immunosorbent assays. Omalizumab inhibited the expression and of production proinflammatory cytokines and growth factor in antigen-stimulated BECs at 6 and 24 hours. Production of NO was inhibited at 6 hours and increased at 24 hours by omalizumab and budesonide. The effects of omalizumab were similar to those of budesonide. These results, consistent with previously reported evidence of anti-inflammatory effects of omalizumab, demonstrate that omalizumab may reduce airway inflammation and probably contributes to decreased airway remodeling in patients with asthma.