title: Intranasal administration of CpG oligodeoxynucleotides reduces lower airway inflammation in a murine model of combined allergic rhinitis and asthma syndrome.
abstract: Given the relationship between allergic rhinitis (AR) and asthma, it can be hypothesized that reducing upper airway inflammation by targeting oligodeoxynucleotides with CpG motifs (CpG-ODN) specifically to the upper airway via intranasal administration in a small volume (10 μL) might improve lower airway (asthma) outcomes. The goal of this study was to investigate the therapeutic efficacy of 10 μL of intranasal versus intradermal administration of CpG-ODN in suppressing lower airway inflammation and methacholine-induced airway hyperreactivity (AHR) in mice subjected to ovalbumin (OVA)-induced combined allergic rhinitis and asthma syndrome (CARAS). OVA-sensitized BALB/c mice were subjected to upper-airway intranasal OVA exposure three times per week for 3 weeks. Then, CpG-ODN was administered to a subset of these mice 1h after intranasal OVA exposure, followed by five days of OVA aerosol challenges, thereby targeting OVA to the lower airways. Immunologic variables and nasal symptoms were evaluated. The results showed that the CARAS mice exhibited significant increases in bronchoalveolar lavage fluid (BALF) and splenocytes Th2-associated cytokine production, OVA-specific serum IgE, and AHR, as well as nose and lung pathologies. Intranasal administration of CpG-ODN significantly reduced Th2-associated cytokine production, the percentage of eosinophils in the BALF, the IL-4 and IL-5 concentrations in the supernatants of cultured OVA-challenged splenic lymphocytes, the serum OVA-specific IgE levels, the peribronchial inflammation score in the lungs, and the severity of nose pathology and nasal symptoms. However, intradermal administration of CpG-ODN did not significantly reduce the aforementioned parameters. In conclusion, intranasal treatment with CpG-ODN attenuated AR and significantly alleviated lower airway inflammation and AHR in the CARAS model. CpG-ODN therapy was more effective when administered intranasally than when administered intradermally. The current study supports the development of CpG-ODN nasal spray as a novel therapeutic agent for CARAS.
authors.affiliation: Department of Pulmonary Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Li
authors.affiliation: Department of Pulmonary Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, China. Electronic address: zhtituli@163.com.
authors.forename: Tian-Tuo
authors.initials: TT
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhuang-Gui
authors.initials: ZG
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Pulmonary Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pulmonary Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Zou
authors.affiliation: Department of Pulmonary Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Pulmonary Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, China.
authors.forename: Hai-Ling
authors.initials: HL
authors.lastname: Yang
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D008214:Lymphocytes / Q000276:immunology; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010047:Ovalbumin / Q000276:immunology; D065631:Rhinitis, Allergic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013154:Spleen / Q000166:cytology; D013577:Syndrome
chemical_list: D000485:Allergens; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Allergic rhinitis; Bronchial asthma; CpG oligodeoxynucleotides; Cytokines