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.