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*
Division of Allergy and Immunology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555; and
Retroviral Immunology Section, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
Asthma is an inflammatory disease of the airways that is induced by
Th2 cytokines and inhibited by Th1 cytokines. Despite a steady increase
in the incidence, morbidity, and mortality from asthma, no current
treatment can reduce or prevent asthma for a prolonged period. We
examined the ability of unmethylated CpG oligodeoxynucleotides (ODN),
which are potent inducers of Th1 cytokines, to prevent the inflammatory
and physiological manifestations of asthma in mice sensitized to
ragweed allergen. Administration of CpG ODN 48 h before allergen
challenge increased the ratio of IFN-
to IL-4 secreting cells,
diminished allergen-induced eosinophil recruitment, and decreased the
number of ragweed allergen-specific IgE-producing cells. These effects
of CpG ODN were sustained for at least 6 wk after its administration.
Furthermore, there was a vigorous Th1 memory response to the recall Ag,
inhibition of peribronchial and perivascular lung inflammation, and
inhibition of bronchial hyperresponsiveness 6 wk after administration
of CpG ODN. Administration of CpG ODN in IFN- -/- mice failed to
inhibit eosinophil recruitment, indicating a critical role of IFN-
in mediating these effects. This is the first report of a treatment
that inhibits allergic lung inflammation in presensitized animals for a
prolonged period and thus has relevance to the development of an
effective long term treatment for asthma.
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R. K. Ikeda, J. Nayar, J. Y. Cho, M. Miller, M. Rodriguez, E. Raz, and D. H. Broide Resolution of Airway Inflammation following Ovalbumin Inhalation: Comparison of ISS DNA and Corticosteroids Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 655 - 663. [Abstract] [Full Text] [PDF]
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J. D. Marshall, K. Fearon, C. Abbate, S. Subramanian, P. Yee, J. Gregorio, R. L. Coffman, and G. Van Nest Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions J. Leukoc. Biol., June 1, 2003; 73(6): 781 - 792. [Abstract] [Full Text] [PDF]
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G. Wohlleben, J. Muller, U. Tatsch, C. Hambrecht, U. Herz, H. Renz, E. Schmitt, H. Moll, and K. J. Erb Influenza A Virus Infection Inhibits the Efficient Recruitment of Th2 Cells into the Airways and the Development of Airway Eosinophilia J. Immunol., May 1, 2003; 170(9): 4601 - 4611. [Abstract] [Full Text] [PDF]
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B. K. Choudhury, J. S. Wild, R. Alam, D. M. Klinman, I. Boldogh, N. Dharajiya, W. J. Mileski, and S. Sur In Vivo Role of p38 Mitogen-Activated Protein Kinase in Mediating the Anti-inflammatory Effects of CpG Oligodeoxynucleotide in Murine Asthma J. Immunol., November 15, 2002; 169(10): 5955 - 5961. [Abstract] [Full Text] [PDF]
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 K. Kitagaki, V. V. Jain, T. R. Businga, I. Hussain, and J. N. Kline Immunomodulatory Effects of CpG Oligodeoxynucleotides on Established Th2 Responses Clin. Vaccine Immunol., November 1, 2002; 9(6): 1260 - 1269. [Abstract] [Full Text] [PDF]
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J. N. Kline, K. Kitagaki, T. R. Businga, and V. V. Jain Treatment of established asthma in a murine model using CpG oligodeoxynucleotides Am J Physiol Lung Cell Mol Physiol, July 1, 2002; 283(1): L170 - L179. [Abstract] [Full Text] [PDF]
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M. Gursel, D. Verthelyi, I. Gursel, K. J. Ishii, and D. M. Klinman Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide J. Leukoc. Biol., May 1, 2002; 71(5): 813 - 820. [Abstract] [Full Text] [PDF]
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H. Renz and U. Herz The bidirectional capacity of bacterial antigens to modulate allergy and asthma Eur. Respir. J., January 1, 2002; 19(1): 158 - 171. [Abstract] [Full Text] [PDF]
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N. P. Juffermans, J. C. Leemans, S. Florquin, A. Verbon, A. H. Kolk, P. Speelman, S. J. H. van Deventer, and T. van der Poll CpG Oligodeoxynucleotides Enhance Host Defense during Murine Tuberculosis Infect. Immun., January 1, 2002; 70(1): 147 - 152. [Abstract] [Full Text] [PDF]
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K. Blease, C. Jakubzick, J. M. Schuh, B. H. Joshi, R. K. Puri, and C. M. Hogaboam IL-13 Fusion Cytotoxin Ameliorates Chronic Fungal-Induced Allergic Airway Disease in Mice J. Immunol., December 1, 2001; 167(11): 6583 - 6592. [Abstract] [Full Text] [PDF]
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Z. K. Ballas, A. M. Krieg, T. Warren, W. Rasmussen, H. L. Davis, M. Waldschmidt, and G. J. Weiner Divergent Therapeutic and Immunologic Effects of Oligodeoxynucleotides with Distinct CpG Motifs J. Immunol., November 1, 2001; 167(9): 4878 - 4886. [Abstract] [Full Text] [PDF]
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I. Gursel, M. Gursel, K. J. Ishii, and D. M. Klinman Sterically Stabilized Cationic Liposomes Improve the Uptake and Immunostimulatory Activity of CpG Oligonucleotides J. Immunol., September 15, 2001; 167(6): 3324 - 3328. [Abstract] [Full Text] [PDF]
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K. H. Baek, S. J. Ha, and Y. C. Sung A Novel Function of Phosphorothioate Oligodeoxynucleotides as Chemoattractants for Primary Macrophages J. Immunol., September 1, 2001; 167(5): 2847 - 2854. [Abstract] [Full Text] [PDF]
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 M. Hafner, R. Zawatzky, C. Hirtreiter, W. A. Buurman, B. Echtenacher, T. Hehlgans, and D. N. Mannel Antimetastatic Effect of CpG DNA Mediated by Type I IFN Cancer Res., July 1, 2001; 61(14): 5523 - 5528. [Abstract] [Full Text] [PDF]
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S. Jilek, C. Barbey, F. Spertini, and B. Corthesy Antigen-Independent Suppression of the Allergic Immune Response to Bee Venom Phospholipase A2 by DNA Vaccination in CBA/J Mice J. Immunol., March 1, 2001; 166(5): 3612 - 3621. [Abstract] [Full Text] [PDF]
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F.-G. Zhu and J. S. Marshall CpG-containing oligodeoxynucleotides induce TNF-{alpha} and IL-6 production but not degranulation from murine bone marrow-derived mast cells J. Leukoc. Biol., February 1, 2001; 69(2): 253 - 262. [Abstract] [Full Text]
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Z. Peng, H. Wang, X. Mao, K. T. HayGlass, and F. E. R. Simons CpG oligodeoxynucleotide vaccination suppresses IgE induction but may fail to down-regulate ongoing IgE responses in mice Int. Immunol., January 1, 2001; 13(1): 3 - 11. [Abstract] [Full Text] [PDF]
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D. Serebrisky, A. A. Teper, C.-K. Huang, S.-Y. Lee, T.-F. Zhang, B. H. Schofield, M. Kattan, H. A. Sampson, and X.-M. Li CpG Oligodeoxynucleotides Can Reverse Th2-Associated Allergic Airway Responses and Alter the B7.1/B7.2 Expression in a Murine Model of Asthma J. Immunol., November 15, 2000; 165(10): 5906 - 5912. [Abstract] [Full Text] [PDF]
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F. Meyer, K. T. Wilson, and S. P. James Modulation of Innate Cytokine Responses by Products of Helicobacter pylori Infect. Immun., November 1, 2000; 68(11): 6265 - 6272. [Abstract] [Full Text] [PDF]
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 D. Miyazaki, G. Liu, L. Clark, and S. J. Ono Prevention of Acute Allergic Conjunctivitis and Late-Phase Inflammation with Immunostimulatory DNA Sequences Invest. Ophthalmol. Vis. Sci., November 1, 2000; 41(12): 3850 - 3855. [Abstract] [Full Text]
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D. P. Sester, S. Naik, S. J. Beasley, D. A. Hume, and K. J. Stacey Phosphorothioate Backbone Modification Modulates Macrophage Activation by CpG DNA J. Immunol., October 15, 2000; 165(8): 4165 - 4173. [Abstract] [Full Text] [PDF]
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G. B. Lipford, T. Sparwasser, S. Zimmermann, K. Heeg, and H. Wagner CpG-DNA-Mediated Transient Lymphadenopathy Is Associated with a State of Th1 Predisposition to Antigen-Driven Responses J. Immunol., August 1, 2000; 165(3): 1228 - 1235. [Abstract] [Full Text] [PDF]
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H. Shirota, K. Sano, T. Kikuchi, G. Tamura, and K. Shirato Regulation of Murine Airway Eosinophilia and Th2 Cells by Antigen-Conjugated CpG Oligodeoxynucleotides as a Novel Antigen-Specific Immunomodulator J. Immunol., June 1, 2000; 164(11): 5575 - 5582. [Abstract] [Full Text] [PDF]
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J. Todt, J. Sonstein, T. Polak, G. D. Seitzman, B. Hu, and J. L. Curtis Repeated Intratracheal Challenge with Particulate Antigen Modulates Murine Lung Cytokines ,2 J. Immunol., April 15, 2000; 164(8): 4037 - 4047. [Abstract] [Full Text] [PDF]
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J. S. Wild, A. Sigounas, N. Sur, M. S. Siddiqui, R. Alam, M. Kurimoto, and S. Sur IFN-{gamma}-Inducing Factor (IL-18) Increases Allergic Sensitization, Serum IgE, Th2 Cytokines, and Airway Eosinophilia in a Mouse Model of Allergic Asthma J. Immunol., March 1, 2000; 164(5): 2701 - 2710. [Abstract] [Full Text] [PDF]
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H. Shirota, K. Sano, T. Kikuchi, G. Tamura, and K. Shirato Regulation of T-helper Type 2 Cell and Airway Eosinophilia by Transmucosal Coadministration of Antigen and Oligodeoxynucleotides Containing CpG Motifs Am. J. Respir. Cell Mol. Biol., February 1, 2000; 22(2): 176 - 182. [Abstract] [Full Text]
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Y. Shibata, L. A. Foster, J. F. Bradfield, and Q. N. Myrvik Oral Administration of Chitin Down-Regulates Serum IgE Levels and Lung Eosinophilia in the Allergic Mouse J. Immunol., February 1, 2000; 164(3): 1314 - 1321. [Abstract] [Full Text] [PDF]
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M. G. Chiaramonte, M. Hesse, A. W. Cheever, and T. A. Wynn CpG Oligonucleotides Can Prophylactically Immunize Against Th2-Mediated Schistosome Egg-Induced Pathology by an IL-12-Independent Mechanism J. Immunol., January 15, 2000; 164(2): 973 - 985. [Abstract] [Full Text] [PDF]
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P. Parronchi, F. Brugnolo, F. Annunziato, C. Manuelli, S. Sampognaro, C. Mavilia, S. Romagnani, and E. Maggi Phosphorothioate Oligodeoxynucleotides Promote the In Vitro Development of Human Allergen-Specific CD4+ T Cells into Th1 Effectors J. Immunol., December 1, 1999; 163(11): 5946 - 5953. [Abstract] [Full Text] [PDF]
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