Sustained Suppression of IL-13 by a Vaccine Attenuates Airway Inflammation and Remodeling in Mice
| Autor: | Carolyn R. Weiss, Kent T. HayGlass, Andrew J. Halayko, Allan B. Becker, Qingdong Guan, Yanbing Ma, Allan G. Ma, Richard Warrington, Zhikang Peng, Sujata Basu |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_treatment Clinical Biochemistry Inflammation Bronchoconstrictor Agents Mice Airway resistance medicine Animals Lung Molecular Biology Methacholine Chloride Mice Inbred BALB C Vaccines Interleukin-13 medicine.diagnostic_test biology business.industry Airway Resistance Vaccination Cell Biology respiratory system Asthma Elasticity respiratory tract diseases Ovalbumin Bronchoalveolar lavage medicine.anatomical_structure Cytokine Interleukin 13 Immunology biology.protein Airway Remodeling Cytokines Female Collagen medicine.symptom business Airway Bronchoalveolar Lavage Fluid |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 48:540-549 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/rcmb.2012-0060oc |
| Popis: | We previously reported that a recombinant IL-13 peptide-based virus-like particle vaccine significantly suppressed murine acute airway allergic inflammatory responses. The impact of this strategy on the development of chronic airway inflammation and remodeling has not been investigated. We evaluated whether the vaccine-mediated sustained suppression of IL-13 attenuates features of chronic airway inflammation and remodeling in mice repeatedly challenged with allergen. BALB/c mice received two intraperitoneal sensitizing injections of ovalbumin (OVA) and alum, followed by six consecutive 2-day intranasal OVA challenges at 12-day intervals and then a 4-week recovery period. Anti-IL-13 antibodies were induced with a vaccine before (preventive experiments) or after (interventional experiments) the OVA challenge commenced. Respiratory mechanics were assessed using low-frequency forced oscillation with a small animal ventilator. Cytokine concentrations in bronchoalveolar lavage fluid (BALF) and lung histology were also assessed. In the preventive experiments, vaccination significantly suppressed IL-13 concentrations, the accumulation of inflammatory cells in BALF, lung mucus production, and collagen deposition. Furthermore, vaccination significantly attenuated OVA challenge-induced increases in airway resistance, tissue resistance, and tissue elastance, both acutely and after a 4-week recovery from allergen challenges. In the interventional experiments, vaccination decreased IL-13, TGF-β1, and IL-12p40 concentrations in BALF, as well as mucus production and collagen deposition. Chronic inflammation and sustained airway hyperresponsiveness were not significantly reversed. The persistent suppression of IL-13 with a vaccine inhibits chronic airway inflammation and the development of several key components of airway remodeling, and this intervention is more effective at early stages than later during chronic inflammation. |
| Databáze: | OpenAIRE |
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