Intralymphatic Administration of Metagonimus yokogawai-Extracted Protein Attenuates Experimental Murine Allergic Rhinitis Model

Objectives: This study aimed to evaluate potential therapeutic effect of Metagonimus yokogawai on the OVA-induced allergic rhinitis model. Methods: OVA-sensitized mice were used to assess potential therapeutic effect of the extract protein of M. yokogawai (My-TP). My-TP was administrated via the intralymphatic route to cervical lymph nodes. The frequencies of sneezing or nasal rubbing were recorded. Histopathologic evaluation was performed for eosinophil infiltrations in the tissues of the nasal mucosa and skin. The mRNA relative expressions of the cytokine profiles including Th1, Th2, Th17, and Treg subsets in the nasal mucosa, cervical lymph nodes, and spleen were analyzed by quantitative real-time reverse-transcriptase polymerase chain reaction. The potential underlying mechanism was investigated by examining cytokine profiles including IL-4 and Treg subsets from lymphocytes of the spleen by flow cytometry. Results: Intralymphatic injection of My-TP reduced allergic symptoms and eosinophil infiltration in the nasal mucosa. My-TP-treated group showed markedly decreased levels of OVA-specific IgE and WBC counts in nasal lavage. My-TP-treated group showed the decreased expression levels of IL-4, while those of IL-10 were increased in both the nasal mucosa. The levels of IFN-γ and IL-17 were also decreased in the nasal mucosa and cervical lymph nodes. The immunological mechanism may involve the downregulation of Th2 response and upregulation of Tregs in the nasal mucosa and cervical lymph nodes. Conclusions: Our results provide the first evidence of potential therapeutic effect of M. yokogawai in OVA-sensitized allergic rhinitis mice, suggesting that a Treg/Th2 reorganization may play a role in clinical course of allergic rhinitis.

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T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa

Journal of Leukocyte Biology ◽

10.1189/jlb.0306176 ◽

2006 ◽

Vol 80 (4) ◽

pp. 797-801 ◽

Cited By ~ 105

Author(s):

Jana Goldmann ◽

Erik Kwidzinski ◽

Christine Brandt ◽

Jacqueline Mahlo ◽

Daniel Richter ◽

...

Keyword(s):

T Cells ◽

Lymph Nodes ◽

Nasal Mucosa ◽

Cervical Lymph Nodes

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Evaluation of the Pharmacokinetics of Intranasal Drug Delivery for Targeting Cervical Lymph Nodes in Rats

Pharmaceutics ◽

10.3390/pharmaceutics13091363 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1363

Author(s):

Tomoyuki Furubayashi ◽

Daisuke Inoue ◽

Shunsuke Kimura ◽

Akiko Tanaka ◽

Toshiyasu Sakane

Keyword(s):

Lymph Nodes ◽

Nasal Cavity ◽

Nasal Mucosa ◽

Intranasal Administration ◽

Systemic Circulation ◽

Nasal Delivery ◽

Pharmacokinetic Analysis ◽

Cervical Lymph Nodes ◽

Lymphatic Network ◽

Model Drug

A well-developed lymphatic network is located under the nasal mucosa, and a few drugs that permeate the nasal mucosa are absorbed into the lymphatic capillaries. Lymph from the nasal cavity flows to the cervical lymph nodes (CLNs). In this study, we evaluated the pharmacokinetics of the direct transport of intranasally administered drugs to CLNs through the nasal mucosa of Wistar rats using methotrexate as a model drug. The drug targeting index, which was calculated based on the areas under the concentration–time curves after intravenous and intranasal administration, was 3.78, indicating the benefits of nasal delivery of methotrexate to target CLNs. The direct transport percentage, which was indicative of the contribution of the direct nose–CLN pathway of methotrexate after intranasal administration, was 74.3%. The rate constant of methotrexate from the nasal cavity to CLNs was 0.0047 ± 0.0013 min−1, while that from systemic circulation to CLNs was 0.0021 ± 0.0009 min−1. Through pharmacokinetic analysis, this study demonstrated that the direct nasal–CLN pathway contributed more to the transport of methotrexate to the CLNs than the direct blood–CLN pathway.

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In Vivo Activation of Naive CD4+ T Cells in Nasal Mucosa-Associated Lymphoid Tissue following Intranasal Immunization with Recombinant Streptococcus gordonii

Infection and Immunity ◽

10.1128/iai.74.5.2760-2766.2006 ◽

2006 ◽

Vol 74 (5) ◽

pp. 2760-2766 ◽

Cited By ~ 23

Author(s):

Donata Medaglini ◽

Annalisa Ciabattini ◽

Anna Maria Cuppone ◽

Caterina Costa ◽

Susanna Ricci ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Lymph Nodes ◽

Nasal Mucosa ◽

T Cell Activation ◽

Lymphoid Tissue ◽

Streptococcus Gordonii ◽

Cervical Lymph Nodes ◽

Intranasal Immunization

ABSTRACT The antigen-specific primary activation of CD4+ T cells was studied in vivo by adoptive transfer of ovalbumin-specific transgenic T cells (KJ1-26+ CD4+) following intranasal immunization with recombinant Streptococcus gordonii. A strain of S. gordonii expressing on its surface a model vaccine antigen fused to the ovalbumin (OVA) peptide from position 323 to 339 was constructed and used to study the OVA-specific T-cell activation in nasal mucosa-associated lymphoid tissue (NALT), lymph nodes, and spleens of mice immunized by the intranasal route. The recombinant strain, but not the wild type, activated the OVA-specific CD4+ T-cell population in the NALT (89% of KJ1-26+ CD4+ T cells) just 3 days following immunization. In the cervical lymph nodes and in the spleen, the percentage of proliferating cells was initially low, but it reached the peak of activation at day 5 (90%). This antigen-specific clonal expansion of KJ1-26+ CD4+ T cells after intranasal immunization was obtained with live and inactivated recombinant bacteria, and it indicates that the NALT is the site of antigen-specific T-cell priming.

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D-Pinitol Attenuated Ovalbumin-induced Allergic Rhinitis in Experimental Mice Via Balancing Th1/Th2 Response

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v20i6.8017 ◽

2021 ◽

Author(s):

Xiying You ◽

Xiaopeng Sun ◽

Junfei Kong ◽

Jifeng Tian ◽

Yanping Shi ◽

...

Keyword(s):

Allergic Rhinitis ◽

Immune Responses ◽

Nasal Mucosa ◽

Potential Effect ◽

Ar Model ◽

Cytokine Signaling ◽

Control Group ◽

Th2 Response ◽

T Box ◽

Th1 Immune Responses

Allergic rhinitis (AR) is a complex, chronic immunoinflammatory disorder of the membrane lining of the nasal mucosa. D-Pinitol is considered a cyclic polyol with a potential effect against various allergies. In the present study, we evaluated the anti-allergic effect of pinitol on ovalbumin (OVA)-induced AR model in mice. BALB/c mice were initially sensitized with an intraperitoneal injection of OVA and divided into 5 groups (n=18, in each group) for a treating schedule of distilled water (DW), montelukast (10 mg/kg), and pinitol (5, 10, and 20 mg/kg) through the mouth. Two saline-injected groups were considered as controls by orally administrating DW and pinitol 20. Thereafter, test and control groups were intranasally challenged by OVA and saline, respectively. Our results showed that the OVA challenge caused a marked elevation in AR symptoms like nasal rubbing, sneezing, and discharge which were remarkably diminished using pinitol (10 and 20 mg/kg) and the results were comparable with montelukast. Additionally, increased levels of total and OVA-specific serum Immunoglobulin (Ig) E and IgG1 were significantly attenuated by pinitol as compared to the control group but not the montelukast group. In AR-induced mice, pinitol had significant modulatory effects on representative markers of Th2 (GATA binding protein 3), signal transducer and activator of transcription-6, Interleukins (IL)-4, IL-5, IL-13, suppressors of cytokine signaling 1, Toll-like receptor 4, and myeloid differentiation factor 88), and Type 1 T helper (Th1) immune responses (T-box protein expressed in T cells and Interferon-gamma) as well as the histopathological aberrations induced in the nasal mucosa. In conclusion, Pinitol had potential effects on OVA-induced AR mice through amelioration of nasal symptoms and balancing the Th1/Th2 immune responses during the allergic rhinitis condition.

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Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing CD4+CD25+Foxp3+ T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis Model

Journal of Allergy ◽

10.1155/2012/490905 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Takaya Yamada ◽

Miki Tongu ◽

Kaoru Goda ◽

Noriaki Aoi ◽

Ichiro Morikura ◽

...

Keyword(s):

T Cells ◽

Allergic Rhinitis ◽

Lymph Nodes ◽

Sublingual Immunotherapy ◽

Specific Ige ◽

Regulatory Function ◽

Sublingual Administration ◽

Type I ◽

Cervical Lymph Nodes

Sublingual immunotherapy (SLIT) has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA) followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4+CD25+ regulatory T cells (Tregs), but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN), which strongly suppressed Th2 cytokine production from CD4+CD25− effector T cells in vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4+CD25+Foxp3+ Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.

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Nasal Administration of Lipopolysaccharide Exacerbates Allergic Rhinitis through Th2 Cytokine Production from Mast Cells

Allergies ◽

10.3390/allergies1040020 ◽

2021 ◽

Vol 1 (4) ◽

pp. 216-224

Author(s):

Noriaki Aoi ◽

Takafumi Fuchiwaki ◽

Ichiro Morikura ◽

Hideyuki Kawauchi ◽

Tatsunori Sakamoto

Keyword(s):

Allergic Rhinitis ◽

Clinical Practice ◽

Mast Cells ◽

Nasal Mucosa ◽

Cytokine Production ◽

Nasal Administration ◽

Eosinophil Infiltration ◽

Dependent Manner ◽

Th2 Cytokine ◽

Nasal Symptoms

Background: Microbial infection or exposure to endotoxin later in life exacerbates established asthma. Mast cells are involved in the exacerbation of asthma. This exacerbation involves a toll-like receptor (TLR)–mediated response of mast cells. In the clinical practice of otolaryngology, otolaryngologists experience an exacerbation of nasal congestion when infectious rhinitis develops in patients with allergic rhinitis, but the mechanisms are unknown. Therefore, this study investigated the effect of lipopolysaccharide (LPS) on allergic rhinitis using a mouse allergic rhinitis model. Methods: Female BALB/c mice, TLR4 gene mutant C3H/HeJ mice or mast cell–deficient WBB6F1-W/Wv mice were sensitized intraperitoneally with ovalbumin (OVA)/alum, and were intranasal challenged with OVA and/or LPS. Nasal symptoms and histologic changes were examined. Cytokines in nasal tissue were examined by Western blot. The effects of LPS on degranulation and cytokine production of bone marrow–derived mast cells (BMMCs) were investigated. Results: Nasal administration of LPS together with the antigen exacerbated nasal symptoms, eosinophil infiltration of the nasal mucosa, and increased IL-5 production in the nasal mucosa. It was not observed in C3H/HeJ mice and WBB6F1-W/Wv mice. The addition of LPS increased the production of IL-5 from BMMCs in a dose-dependent manner, but no effect on degranulation was observed. Conclusions: Intranasal administration of LPS exacerbates allergic rhinitis through Th2 cytokine production from mast cells. This observation provides clues to the mechanism of exacerbation of allergic rhinitis caused by an infection in daily clinical practice.

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Local Expression of Interleukin-17a is Correlated with Nasal Eosinophilia and Clinical Severity in Allergic Rhinitis

Allergy & Rhinology ◽

10.2500/ar.2014.5.0078 ◽

2014 ◽

Vol 5 (1) ◽

pp. ar.2014.5.0078 ◽

Cited By ~ 13

Author(s):

Seiichiro Makihara ◽

Mitsuhiro Okano ◽

Tazuko Fujiwara ◽

Yohei Noda ◽

Takaya Higaki ◽

...

Keyword(s):

Allergic Rhinitis ◽

Nasal Mucosa ◽

Immunoglobulin E ◽

Inferior Turbinate ◽

Forced Expiratory Volume ◽

Clinical Severity ◽

Eosinophil Infiltration ◽

Total Serum ◽

Blood Eosinophil ◽

Local Expression

Interleukin (IL)-17A is a major cytokine produced by Th17 cells, which are associated with chronic inflammations. The local expression of IL-17A in allergic rhinitis (AR) remains to be characterized. We sought to determine the role of IL-17A expression in human inferior turbinate mucosa in the pathophysiology of AR. Inferior turbinate mucosa was sampled from medical treatment-resistant, surgery-required patients with perennial AR (PAR, n = 21), nonallergic rhinitis with eosinophilia syndrome (NARES, n = 7), and nonallergic hypertrophic rhinitis (HR, n = 13). IL-17A expression was determined with immunohistochemical staining. The mean number of IL-17A+ cells and eosinophils per field were counted. Total serum immunoglobulin E (IgE) levels, blood eosinophil count, and forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio were also examined in each patient. IL-17A was primarily expressed in infiltrating inflammatory cells. The number of IL-17A+ cells in nasal mucosa was significantly higher in the PAR group compared with HR (p = 0.002) and NARES (p = 0.021) groups. There was a significant and positive correlation between the number of IL-17A+ cells and total nasal symptom score (rho = 0.403; p = 0.011), especially sneezing score (rho = 0.471; p = 0.003). The number of IL-17A+ cells was significantly and positively correlated with the degree of eosinophil infiltration (rho = 0.623; p < 0.001), but not with total serum IgE levels (rho = 0.284; p = 0.098), blood eosinophil counts (rho = 0.302; p = 0.056), or FEV1/FVC ratio (rho = 0.092; p = 0.569). The present study provides evidence that IL-17A expression in the nasal mucosa is associated with the pathophysiology of AR, including disease severity and nasal eosinophilia.

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