Immunostimulatory CpG Oligonucleotides Abrogate Allergic Susceptibility in a Murine Model of Maternal Asthma Transmission
| Autor: | Lester Kobzik, Alexey V. Fedulov, Adriana S. Leme, Eric S. Silverman, Yuhong Xiang |
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| Rok vydání: | 2005 |
| Předmět: |
CpG Oligodeoxynucleotide
Offspring Immunology Mice Adjuvants Immunologic Pregnancy Respiratory Hypersensitivity medicine Animals Immunology and Allergy Eosinophilia Lung Methacholine Chloride Sensitization Asthma Mice Inbred BALB C Dose-Response Relationship Drug medicine.diagnostic_test business.industry respiratory system medicine.disease Infectious Disease Transmission Vertical respiratory tract diseases Bronchoalveolar lavage medicine.anatomical_structure Oligodeoxyribonucleotides CpG site CpG Islands Female Methacholine Disease Susceptibility medicine.symptom business medicine.drug |
| Zdroj: | The Journal of Immunology. 175:4292-4300 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.175.7.4292 |
| Popis: | We tested the potential of CpG oligodeoxynucleotides (ODN) to reverse the increased susceptibility to allergic airways disease in neonatal mice in a model of maternal transmission of asthma risk. Offspring of OVA-sensitized and challenged BALB/c mother mice were subjected to an intentionally suboptimal sensitization protocol that has minimal effects on normal mice, but results in airway hyperresponsiveness (AHR) and airway inflammation (AI) in babies of asthmatic mother mice. We evaluated pulmonary function and AI in CpG- or control ODN-treated offspring. CpG treatment of neonates on day 4 of life prevents the AHR otherwise seen in this model (enhanced pause at 100 mg/ml methacholine: CpG, 0.9 ± 0.1; ODN control, 3.8 ± 0.6; n = 62; p < 0.005). It also prevented the development of AI, as evident in decreased bronchoalveolar lavage eosinophilia (CpG, 1.2 ± 0.3%; ODN, 31.4 ± 4.1%; n = 56; p < 0.005), diminished the severity of AI on histopathology, and resulted in lower IL-5 levels in bronchoalveolar lavage fluid. The effect of CpG persisted for at least 4–6 wk and was allergen independent. Treatment with CpG just before OVA aerosol challenge also prevented allergic responses. The data support the potential for immunomodulatory therapy with CpG in early life to reduce susceptibility to asthma. |
| Databáze: | OpenAIRE |
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