Human Rhinitis Research Articles

Particulate Matter Exposure and the Changes in Immune Biomarkers: Effects of Biyeom-Go on the Nasal Mucosa of Patients with Allergic Rhinitis and a Particulate Matter-Treated Mouse Model

This study was to investigate the effects of Biyeom-go (BYG, an herbal formula) on immune biomarkers present in the nasal mucosa of patients with allergic rhinitis under exposure to particulate matter 2.5 (PM2.5), and on changes in goblet cells and immune biomarkers in mice under exposure to Korea diesel particulate matter (KDP20). Thirty patients showing characteristic allergic rhinitis symptoms were enrolled in Jeonju-si, Korea, and treated with BYG thrice a day for four weeks. Changes in the expression of immune biomarkers (interleukin 4 (IL-4), IL-5, IL-8, IL-13, IL-33, and thymic stromal lymphopoietin (TSLP) mRNA), total nasal symptom scores (TNSS), mini-rhinitis-specific quality of life questionnaire (RQLQ) results, and visual analog scale scores were evaluated after 4 weeks of treatment. Additionally, the difference in PM2.5 concentrations in the air in Jeonju-si, Korea (November, 2019 ∼ March, 2020), was analyzed to determine the change in TNSS. KDP20 (100 μg/mL) was exposed to C57BL/6 mice for 10 days; 0.05% Nasonex (a positive control, mometasone furoate), or BYG was administrated for 5 days twice a day. The expression of inflammatory factors was detected via qRT-PCR using nasopharynx tissue samples of mice. BYG treatment was found to be associated with significant improvement in total nasal symptoms, especially itching and sneezing (p < 0.0001), and mini-RQLQ after 4 weeks. IL-8 (p < 0.01), IL-33 (p < 0.01), and TSLP (p < 0.001) expression levels decreased after BYG treatment. In mice, administration of BYG reduced the number of goblet cells increased through KDP20 treatment. KDP20-induced immune biomarkers (IL-33, TSLP, tumor necrosis factor alpha, and IL-8) were also significantly downregulated in the nasopharynx tissue after BYG treatment. Therefore, BYG may show therapeutic effects against allergic rhinitis in humans, and it was confirmed that the expression of PM-induced inflammatory factors in mice was decreased via BYG treatment.

Intranasal levels of lead as an exacerbation factor for allergic rhinitis in humans and mice

Air pollutants are suspected to affect pathological conditions of allergic rhinitis (AR). After detecting Pb (375 μg/kg) in Japanese cedar pollen, the effects of intranasal exposure to Pb on symptoms of AR were investigated. Pollen counts, subjective symptoms, and Pb levels in nasal epithelial lining fluid (ELF) were investigated in 44 patients with Japanese cedar pollinosis and 57 controls from preseason to season. Effects of intranasal exposure to Pb on symptoms were confirmed by using a mouse model of AR. Pb levels in ELF from patients were >40% higher than those in ELF from control subjects during the pollen season but not before the pollen season. Pb level in ELF was positively associated with pollen counts for the latest 4 days before visiting a hospital as well as scores of subjective symptoms. Intranasal exposure to Pb exacerbated symptoms in allergic mice, suggesting Pb as an exacerbation factor. Pb levels in ELF and nasal mucosa in Pb-exposed allergic mice were higher than those in Pb-exposed nonallergic mice, despite intranasally challenging the same amount of Pb. Because the increased Pb level in the nasal mucosa of Pb-exposed allergic mice was decreased after washing the nasal cavity, Pb on the surface of but not inside the nasal mucosa may have been a source of increased Pb level in ELF of allergic mice. Increased nasal Pb level partially derived from pollen could exacerbate subjective symptoms of AR, indicating Pb as a novel hazardous air pollutant for AR.

Expression and refolding of mite allergen pro-Der f1 from inclusion bodies in Escherichia coli

House dust mite (Dermatophagoides farinae) allergen Der f1 is one of the most important indoor allergens associated with asthma, eczema and allergic rhinitis in humans. Therefore, sufficient quantities of Der f1 cysteine protease to be used for both experimental and therapeutic purposes are very much needed. Using recombinant DNA technology, high expression rates of cysteine proteases were obtained. The cDNA sequence encoding pro-Der f1 was cloned and expressed in Escherichia coli using the T7 based expression vector pET-44a and induced by isopropyl-β-d-thiogalactoside at a final concentration of 0.2mM. Recombinant pro-Der f1 (pro-rDer f1) was expressed as an inclusion body and the isolated protease was solubilized, refolded and purified. The protease activities and IgE reactivities of pro-rDer f1 that were refolded by size-exclusion chromatography (SEC) were higher than those obtained by dilution. The pair of pro-rDer f1 polypeptides produced by this method could be used for more effective and safer allergen-specific immunotherapy or to produce enzymatically and immunologically active Der f1 for diagnostic testing and deciphering of immunotherapy mechanisms.

Effect of IL-15 on IgG versus IgE antibody-secreting cells in vitro

Immunoglobulin E (IgE) antibodies are major contributors to the pathology of atopic and allergic diseases as well as to immune response to helminth infections. Development of an adequate immunoglobulin G (IgG) immune response against infectious agents and vaccine antigens is considered in most cases as crucial for protection from disease. In vivo and in vitro production of IgE and IgG depends on cytokines and other soluble factors. Recently it has been shown that IgG antibody secreting cells (ASCs) can be generated by in vitro maturation of blood cells with Interleukin- (IL-)15 and CpG DNA or other stimulation cocktails, while IgE-ASCs develop upon cultivation with anti-CD40 and IL-4.In the present study we employed an enzyme linked immunospot assay (ELISPOT) to assess the capacity of individuals to develop into either IgE-ASCs or IgG-ASCs upon stimulation with different combinations of stimulation cocktails in order to investigate the influence of cytokines that are dysregulated in IgE-mediated immune reactions on ASC generation.Furthermore, we modified the method to assess IgG- and IgE-ASCs specific for two model antigens causing allergic rhinitis in humans. We demonstrate that IL-15, which is important for development of IgG-ASCs, decreases the number of IgE-ASCs when added to media commonly used for in vitro development of IgE-ASCs. We show that our method is suitable for the detection of specific and non-specific IgE-ASCs and IgG-ASCs and allows the investigation of the interplay between IgG-ASCs and IgE-ASCs in different populations.

Nasal Mucosal TRPA1 and TRPV1 Levels in Human Rhinitis

Nasal Mucosal TRPA1 and TRPV1 Levels in Human Rhinitis

Prophylactic Effects of the Histamine H1 Receptor Antagonist Epinastine and the Dual Thromboxane A2 Receptor and Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells Antagonist Ramatroban on Allergic Rhinitis Model in Mice

The prophylactic use of anti-allergic drugs has been proposed to be effective in the treatment of seasonal allergic rhinitis in humans. However, there is little information regarding the prophylactic effect of thromboxane A(2) (TXA(2)) receptor antagonist on allergic rhinitis. Recent studies revealed that a TXA(2) receptor antagonist ramatroban could block the prostaglandin D(2) (PGD(2)) receptor and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). In the present study, we investigated the prophylactic effects of the histamine H(1) receptor antagonist epinastine and the TXA(2) receptor antagonist ramatroban and seratrodast on mouse models of allergic rhinitis. Female BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin and alum on days 0, 5, 14 and 21. Seven days later, mice were sensitized by intranasal application of ovalbumin thrice a week. Drugs were administered once a day from day 22. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms (sneezing and nasal rubbing). Histamine sensitivity and eosinophil infiltration into the nasal mucosa were also determined. Epinastine and ramatroban significantly reduced nasal symptoms and the number of eosinophils in the nasal mucosa. Seratrodast showed no effect on nasal symptoms and eosinophil infiltration into the nasal mucosa. In addition, histamine sensitivity was reduced by epinastine and ramatroban. These results indicate that epinastine and ramatroban induce the prophylactic effect on allergic rhinitis.

Conidiobolomicose em ovinos: reavaliação de três casos previamente diagnosticados como tumor etimoidal enzoótico

Conidiobolomycosis is an infection caused by fungi of the genus Conidiobolus spp. that is associated with a granulomatous rhinitis in humans and animals. In sheep, the disease is clinically characterized by respiratory changes, exophthalmia, craniofacial asymmetry, and fever. Microscopically, there are multifocal granulomas containing intralesional hyphae. For a long time, this disease was diagnosed as Enzootic Ethmoid Tumor. This report described three cases of conidiobolomycosis that had been previously diagnosed as Enzootic Ethmoid Tumor. Samples of nasal cavity, lung, parotid gland, and lymph node from three sheep submitted to histopathological examination in 1979 were retrieved in 2010 for a new histological, histochemical, and immunohistochemical evaluations. Paraffin-embedded tissue sections were stained with Hematoxylin-Eosin, Grocott's Metanamine Silver, and Periodic Acid Schiff. Immunohistochemistry was performed on paraffin embedded tissues using anti-cytokeratin primary antibody. Based on histopathology, histochemistry, and immunohistochemistry, the diagnosis of conidiobolomycosis was confirmed in three sheep, which had been previously diagnosed as Enzootic Ethmoid Tumor in 1979.

Rodent models of allergic rhinitis: Relevance to human pathophysiology

Rodent models of allergic airways disease employ a wide range of test allergens, sensitization and provocation protocols, animal strains, and experimental endpoints. Studies of experimental asthma, especially the use of murine models, have contributed significantly to the understanding of the genetics and immune-mediated pathophysiology of pulmonary airways during allergy. By comparison, rodent models of allergic rhinitis are less well developed. Recent interest in the potential mechanistic links between asthma and allergic rhinitis has increased the need for relevant animal studies directed at upper airways responses. Specifically, the nature of nasal airway remodeling in response to chronic activation of allergic pathways and its relationship to airway occlusion is not well described. This cursory review discusses current approaches to assessing nasal obstruction in rodent models, and how the histopathologic analysis might be improved to facilitate understanding of the pathogenesis of allergic rhinitis in humans.

MRNA Induction and Cytokine Release of Inflammatory Mediators During In Vitro Exposure of Human Nasal Respiratory Epithelia to Acetaldehyde

Acetaldehyde has been shown to be cytotoxic and carcinogenic to the upper respiratory tract epithelium of rodents following long-term exposure. Most animal studies have concentrated on carcinogenicity and DNA–protein cross-link formation, while less is known about potential dose- and time-dependent induction of aldehyde-induced rhinitis in humans. In this in vitro study, 22 primary cell cultures established from inferior turbinate tissue of healthy individuals were exposed to acetaldehyde concentrations of 50 (German MAK value) or 500 ppm for 4 or 24 h. mRNA expression and protein levels of cytokines and other inflammatory mediators were quantified at the end of the 4- and 24-h exposures. Controls were exposed to synthetic air. Quantitative polymerase chain reaction (Q-PCR) analysis was performed for interleukin (IL)-6, IL-8, IL-1β, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-alpha, GMCSF, Cox-1, and Cox-2. Enzyme-linked immunosorbent assay (ELISA) was performed from culture supernatants for IL-6, IL-8, IL-1β, MCP-1, TNF-alpha, and GMCSF. Significant inductions of IL-1β, TNF-alpha, and Cox-1 and Cox-2 mRNA were observed following exposure to ≥50 ppm acetaldehyde for 4 h. IL-6 and MCP-1 were also induced following a 4-h exposure to 500 ppm acetaldehyde. For all these parameters, effects were significantly stronger at the higher concentration. After 24-h of exposure only Cox-2 remained significantly elevated at 500 ppm but not at 50 ppm, while all other mediators had been downregulated. The obtained data suggest that with exposure to 500 ppm and remarkably also at the level of the occupational exposure limit of 50 ppm, an immediate transient upregulation of inflammatory mediator mRNA is induced, possibly leading to subclinical inflammatory effects.

Antigen-Specific T Cell Tolerance Down-Regulates Mast Cell Responses in Vivo

Fel d I is the major cat allergen that induces asthma and allergic rhinitis in humans. To investigate the mechanism of allergic responses to this allergen, a mouse model was developed. Mice sensitized to chain 1 of Fel d I exhibited T cell responses, B cell responses, and mast cell responses when challenged with the protein. Subcutaneous injections of peptides containing the dominant T cell epitopes of the allergen induced T cell tolerance in presensitized mice. When challenged with the allergen intratracheally, these tolerized mice produced a decreased amount of histamine in vivo. The decrease in histamine release was not solely dependent on the reduction of allergen-specific IgE. These data show that mast cell activity in mice with an ongoing sensitivity to allergen can be regulated through peptide-induced T cell tolerance.

Pavlovian conditioning of nasal tryptase release in human subjects with allergic rhinitis

The role of Pavlovian conditioning in humans with perennial allergic rhinitis was investigated using release of tryptase from sensitised mast cells as an indicator of allergic responsiveness. Challenge with house dust mite allergen (unconditioned stimulus) was paired with a drink of novel taste and appearance (conditioned stimulus) in a single conditioning trial. Upon reexposure to the conditioned stimulus alone, levels of mast cell tryptase released in subjects who had received both the novel drink and allergen challenge on the conditioning trial was significantly greater than subjects who had received either the drink or the allergen alone. The results support the involvement of the central nervous system in mast cell degranulation in allergic rhinitis in humans.

Effects of nedocromil sodium on allergen-induced rhinitis in humans

Sixteen patients with allergic rhinitis were recruited into a double-blind crossover protocol studying the immediate effect of nedocromil sodium (NS) on the pattern of nasal symptoms and secretions after allergen challenge. After pretreatment with placebo or NS, allergen challenge resulted in pruritus, rhinorrhea, nasal congestion, and/or sneezing within 10 minutes in 12 of 16 subjects. Prostaglandin D 2 (PGD 2), a marker of mast cell degranulation, increased proportionately with symptom scores, remaining above the 95% confidence interval for 120 minutes after both pretreatments. No difference in PGD 2 between the NS-treatment and placebo-treatment days was observed. Protein markers extravasatel through the vasculature (albumin and IgG) or secreted by mucosal glands (lactoferrin) were assayed. Total protein, albumin, IgG, and lactoferrin all remained > 95% confidence interval for 100 minutes after allergen challenge in the placebo-pretreated group and 120 minutes in the NS-pretreated group. Although there appeared to be a trend for lower secretion of PGD 2, albumin, and IgG in the NS-treated group, the overall differences did not achieve statistical significance. This protocol revealed that two topical 130 μl doses of a 1% solution of NS failed to significantly reduce allergen-induced symptoms, PGD 2 generation, or secretion of albumin, IgG, or lactoferrin when NS was compared with placebo. The anti-inflammatory and mast cell-stabilizing effects of NS may require more prolonged pretreatment before provocation to be effective.

64 Effects of nedocrumil sodium on allergen-induced rhinitis in humans

64 Effects of nedocrumil sodium on allergen-induced rhinitis in humans

Ｎｅｗｃａｓｔｌｅ病ウイルス感染ｃｈｉｃｋｅｎ鼻粘膜の形態学的研究

Newcastle disease virus infection following intranasal inoculation of chicks with a mesogenic strain of the virus produced a localized infection of the middle turbinate which was histologically demonstrable 3 days after inoculation. There was destruction of mucous cells of individual acini in the inner surface of the middle turbinate, and the infection spread rapidly to ciliated and goblet cells and to neighboring acini.By day 3, there was undulation or disappearance of the cilia and lymhoid cell infiltraion under epithelium. On day 5 the inflammation in the infected middle turbinate was more severe than on day 3, but by day 7 light microscopy showed almost complete recovery. However, scanning electron microscopy showed cilia of various lengths. The cilia did not return to normal until day 14. On day 21 and thereafter, the mucociliated epithelium was essentially normal.The infection is sequentially similar to acute mild rhinitis in humans.