Allergy Asthma Immunol Res.  2019 Mar;11(2):267-279. 10.4168/aair.2019.11.2.267.

Intranasal Treatment With 1, 25-Dihydroxyvitamin D3 Alleviates Allergic Rhinitis Symptoms in a Mouse Model

• Cho SW
• Zhang YL
• Ko YK
• Shin JM
• Lee JH
• Rhee CS
• Kim DY

• KMID: 2431858
• DOI: http://doi.org/10.4168/aair.2019.11.2.267

Abstract

PURPOSE
Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear.
METHODS
The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay.
RESULTS
In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased.
CONCLUSIONS
The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.

Keyword

Animal model; allergic rhinitis; dendritic cell; intranasal administration; vitamin D; antiallergic agents

MeSH Terms

Administration, Intranasal
Animals
Anti-Allergic Agents
Calcitriol
Cell Proliferation
Dendritic Cells
Eosinophils
Flow Cytometry
Immunoglobulin E
Immunoglobulin G
Immunoglobulins
Inflammation
Interleukin-10
Interleukin-13
Interleukin-4
Interleukin-5
Lymph Nodes
Lymphocytes
Major Histocompatibility Complex
Mice*
Models, Animal
Ovalbumin
Ovum
Rhinitis, Allergic*
RNA, Messenger
Vitamin D
Anti-Allergic Agents
Calcitriol
Immunoglobulin E
Immunoglobulin G
Immunoglobulins
Interleukin-10
Interleukin-13
Interleukin-4
Interleukin-5
Ovalbumin
RNA, Messenger
Vitamin D

Figure

• 

  Fig. 1 Experimental protocol for sensitization with OVA and aluminum hydroxide gel and treatment with 1, 25-dihydroxyvitamin D3. OVA, ovalbumin; PBS, phosphate-buffered saline.

• 

  Fig. 2 Sneezing (left) and nose rubbing (right) bouts within 15 minutes. Intranasal treatment with 1, 25-dihydroxyvitamin D3 (group 3) suppressed allergic symptoms. Data are expressed as the mean ± standard error mean. *P < 0.05.

• 

  Fig. 3 The H&E staining (×400) (left). Arrow heads show eosinophilic granules with 2-lobed nuclei. Intranasal 1, 25-dihydroxyvitamin D3 treatment suppressed eosinophil infiltration in the nasal mucosa (right). Data indicate mean ± standard error mean. H&E, hematoxylin and eosin. *P < 0.05.

• 

  Fig. 4 Decreased IL-4 and IL-13 mRNA levels in the nasal tissue in 1, 25-dihydroxyvitamin D3 treated mice (group 3). Data are expressed as the mean ± standard error mean. IL, interleukin; IFN, interferon. *P < 0.05.

• 

  Fig. 5 (A) Decreased CD86 expression among DCs from mice treated with intranasal 1, 25-dihydroxyvitamin D3. (B, C) No significant difference in proportion (%) of CD86 + DCs or Tregs among the different groups. (D) Example histogram in each group representing expression of CD86 among DCs. Numerical values next to the histogram indicate MFI. Data are expressed as the mean ± standard error mean. DC, dendritic cell; Treg, regulatory T cell; MFI, mean fluorescence intensity; APC, anaphase-promoting complex. *P < 0.05.

• 

  Fig. 6 Cytokine levels in the lymphocyte culture from cervical LNs. Level of IL-4 was significantly decreased in mice treated with intranasal 1, 25-dihydroxyvitamin D3. Data are expressed as the mean ± standard error mean. LN, lymph node; IL, interleukin. *P < 0.05.

• 

  Fig. 7 Levels of serum total IgE and OVA-specific IgE, IgG1, and IgG2a. Data are expressed as the mean ± standard error mean. Ig, immunoglobulin; OVA, ovalbumin. *P < 0.05.

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