Systemic Administration of Olygodeoxynucleotides with CpG Motifs at Priming Phase Reduces Local Th2 Response and Late Allergic Rhinitis in BALB/c Mice

Abstract

Oligodeoxynucleotides (ODN) with CpG motifs (CpG ODN) induce T helper (Th)1-type reaction. We aimed to evaluate the therapeutic effect of CpG ODN in the development of late allergic rhinitis induced by ovalbumin (OVA), which is one of Th2 diseaes, in BALB/c mice. Effects of a single dose of synthetic CpG-ODN (50 microg) intraperitoneally (i.p.) at the priming phase (on day 0) by OVA on the development of late eosinophilic rhinitis at respiratory areas were compared to the control mice treated with its vehicle (ODN without CpG motifs; 50 microg). Animals were again sensitized by OVA (on day 10) i.p., and 4 days after second sensitization animals were challenged by OVA intranasally (on day 14). Four days after challenge, eosinophilic reactions, nasal lesions and local cytokine values were examined. Compared to the control group, the CpG ODN-administration increased production of OVA-specific Th1 cytokine (interferon-gamma) and decreased productions of ovalubmin-specific Th2 cytokines [interleukin (IL)-5 and IL-13] in nasal cavity fluids, supernatants of splenocytes and/or sera. Also, eosinophilia and increased total IgE values were decreased in mice treated with the CpG ODN compared to the control group. Moreover, nasal lesions with infiltration of eosinophils were prominently reduced by the CpG ODN-treatment compared to the control mice. The present study suggests that the systemic administration of CpG ODN at the priming phase may reduce local OVA-specific Th2 responses, resulting in decreased nasal pathology in the late allergic eosinophilic rhinitis.

Acute uriticaria‐like lesions in allergen‐unexposed cutaneous tissues in a mouse model of late allergic rhinitis

“…One might suppose that some of the inflammatory mediators especially histamine produced by the original nasal lesions and circulated in the peripheral blood may contribute to the increased permeability of venules in the dermis and subcutaneous tissues. However, there was no evidence of the increase in the number of mast cells of nasal mucosa under our experimental conditions including our previous studies (Hayashi et al. 2007; Sasaki et al.…”

“…The mice were divided into following two groups. The sensitization and challenge procedures (Figure 1a) were carried out by the methods described previously (Hayashi et al. 2007) with a simple modification.…”

“…In addition, it has never been reported that allergen inhalation challenge causes cutaneous changes in subjects who do not have atopic skin disease (Togias 2004). Thus, we focused on the cutaneous reaction with special reference to the expression of adhesion molecules (CLA, ICAM‐1/LFA‐1 and VCAM‐1/VLA‐4) and distribution of OVA and IgE in a mouse model of late allergic rhinitis (LAR) (Hayashi et al. 2007).…”

SOCS3 drives proteasomal degradation of indoleamine 2,3-dioxygenase (IDO) and antagonizes IDO-dependent tolerogenesis

“…(29), modulation of pathogenic T-helper responses (30)(31)(32), and differentiation toward a regulatory phenotype (33,34).…”

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

“…group), a dose that is known to be optimal for the stimulation of murine cells [25]. Synthetic CpG-ODN containing two CpG motifs (5ˊ-TCCATGACGTTCCTGACGTT-3ˊ) (endotoxin-free and higher than 99% purity; Sangon Biotechnology, Shanghai, China) were used as reported previously [26]. The optimal dosages of CpG-ODN were obtained from a pilot study using different CpG-ODN dosages (2.5, 5.0, 10.0 and 20.0 μg).…”