Abstract
CpG oligodeoxynucleotides (CpG-ODN) administered during Ag sensitization or before Ag challenge can inhibit allergic pulmonary inflammation and airway hyperreactivity in murine models of asthma. In this study, we investigated whether CpG-ODN can reverse an ongoing allergic pulmonary reaction in a mouse model of asthma. AKR mice were sensitized with conalbumin followed by two intratracheal challenges at weekly intervals. CpG-ODN was administered 24 h after the first Ag challenge. CpG-ODN administration reduced Ag-specific IgE levels, bronchoalveolar lavage fluid eosinophils, mucus production, and airway hyperreactivity. We found that postchallenge CpG-ODN treatment significantly increased IFN-gamma concentrations and decreased IL-13, IL-4, and IL-5 concentrations in bronchoalveolar lavage fluids and spleen cell culture supernatants. Postchallenge CpG-ODN treatment also increased B7.1 mRNA expression and decreased B7.2 mRNA expression in lung tissues. These results suggest that CpG-ODN may have potential for treatment of allergic asthma by suppressing Th2 responses during IgE-dependent allergic airway reactions. The down-regulation of Th2 responses by CPG-ODN may be associated with regulation of the costimulatory factors B7.1 and B7.2.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Adjuvants, Immunologic / pharmacology*
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Animals
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Antigens, CD / biosynthesis*
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Antigens, CD / genetics
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Asthma / immunology*
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Asthma / pathology
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B7-1 Antigen / biosynthesis*
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B7-1 Antigen / genetics
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B7-2 Antigen
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Bronchial Hyperreactivity / immunology*
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Cells, Cultured
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Conalbumin / administration & dosage
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Conalbumin / immunology
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CpG Islands / immunology*
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Disease Models, Animal
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Down-Regulation / immunology
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Hyperplasia
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Immunoglobulins / biosynthesis
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Injections, Intraperitoneal
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / biosynthesis
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Interleukin-13 / biosynthesis
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Interleukin-4 / biosynthesis
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Interleukin-5 / biosynthesis
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Male
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / genetics
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Mice
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Mice, Inbred AKR
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Oligodeoxyribonucleotides / administration & dosage
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Oligodeoxyribonucleotides / pharmacology*
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RNA, Messenger / biosynthesis
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Respiratory Mucosa / immunology
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Respiratory Mucosa / pathology
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Th2 Cells / immunology*
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Up-Regulation / immunology
Substances
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Adjuvants, Immunologic
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Antigens, CD
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B7-1 Antigen
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B7-2 Antigen
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CPG-oligonucleotide
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Cd86 protein, mouse
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Immunoglobulins
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Interleukin-13
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Interleukin-5
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Membrane Glycoproteins
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Oligodeoxyribonucleotides
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RNA, Messenger
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Conalbumin
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Interleukin-4
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Interferon-gamma