Intranasal administration of CpG oligodeoxynucleotides reduces lower airway inflammation in a murine model of combined allergic rhinitis and asthma syndrome.

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.

Li HT ，Zhang TT ，Chen ZG ，Ye J ，Liu H ，Zou XL ，Wang YH ，Yang HL ... -  《-》

Treatment of allergic rhinitis with CpG oligodeoxynucleotides alleviates the lower airway outcomes of combined allergic rhinitis and asthma syndrome via a mechanism that possibly involves in TSLP.

Li HT ，Chen ZG ，Liu H ，Ye J ，Zou XL ，Wang YH ，Yang HL ，Meng P ，Zhang TT ... -  《-》

4-1 BB stimulation inhibits allergen-specific immunoglobulin E production and airway hyper-reactivity but partially suppresses bronchial eosinophilic inflammation in a mouse asthma model.

Cho YS ，Kwon B ，Lee TH ，Kim TB ，Moon KA ，La S ，Lee J ，Lee SD ，Oh YM ，Moon HB ... -  《CLINICAL AND EXPERIMENTAL ALLERGY》

Modulation of murine allergic rhinosinusitis by CpG oligodeoxynucleotides.

Hussain I ，Jain VV ，Kitagaki K ，Businga TR ，O'Shaughnessy P ，Kline JN ... -  《LARYNGOSCOPE》

CpG-ODNs and Budesonide Act Synergistically to Improve Allergic Responses in Combined Allergic Rhinitis and Asthma Syndrome Induced by Chronic Exposure to Ovalbumin by Modulating the TSLP-DC-OX40L Axis.

Li HT ，Chen ZG ，Lin YS ，Liu H ，Ye J ，Zou XL ，Wang YH ，Yang HL ，Zhang TT ... -  《-》