Antidepressant Drug, Desipramine, Alleviates Allergic Rhinitis by Regulating Treg and Th 17 Cells

2013 ◽  
Vol 26 (1) ◽  
pp. 107-115 ◽  
Author(s):  
Y. Zhang ◽  
H. Zhen ◽  
W. Yao ◽  
F. Bian ◽  
X. Mao ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Immunoglobulin E ◽  
Antidepressant Drug ◽  
Flow Cytometric Analysis ◽  
Specific Ige ◽  
Tricyclic Antidepressant ◽  
Interleukin 4 ◽  
Therapeutic Effects ◽  
Nasal Symptoms ◽  
Ifn Γ

Allergic rhinitis (AR) is characterized by IgE-mediated immediate hypersensitivity and usually progresses to chronic nasal inflammation, with depression as one of its comorbidities. The importance of treating the depression in AR patients has been increasingly recognized. Desipramine is a representative of tricyclic-antidepressant agents. In the present study we investigate whether desipramine has therapeutic effects on AR inflammation. BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by repeated challenge with OVA intranasally. Desipramine was administered orally to treat the mice. The nasal symptoms (sneezing, nasal scratching etc.) of AR were evaluated to determine the severity of AR. Cytokines in the nasal lavage fluid (NALF), including interferon-γ (IFN-γ), interleukin 4 (IL-4) and serum OVA-specific immunoglobulin E (IgE) antibody were measured by ELISA. The regulatory T cells (Treg) and T helper cells 17 (Th17) were quantified by flow cytometric analysis. As a result, the repeated oral administration of desipramine attenuated the nasal symptoms (sneezing and nasal rubbing) in AR mice. Desipramine also suppressed the serum OVA-specific IgE and IL-4 levels, but had no effect on IFN-γ level. Moreover, desipramine treatment up regulated CD4+CD25+Foxp3+Treg cells, which were found down-regulated in established AR mice. Meanwhile, desipramine administration attenuated CD4+IL-17+ Th17 cells, which were significantly increased in AR mice. These results suggest that the antidepressant drug, desipramine, also has anti-allergic action, which was possibly achieved by reducing allergen-specific IgE and Th2 cytokine production and maintaining a balance between Treg and Th17 cells. Thus, this study provide the first evidence that desipramine may be utilized to treat allergic diseases, especially for those allergic patients with depression or depression patients with allergy.

scholarly journals Apigenin Attenuates Allergic Responses of Ovalbumin-Induced Allergic Rhinitis Through Modulation of Th1/Th2 Responses in Experimental Mice

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090479 ◽  
Author(s):  
Feng Chen ◽  
Dongyun He ◽  
Bailing Yan
Keyword(s):  
Allergic Rhinitis ◽  
Messenger Rna ◽  
Immunoglobulin E ◽  
Elevated Serum ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Cytokine Signaling ◽  
Nuclear Factor ◽  
Th2 Response ◽  
Ifn Γ

Background: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune-inflammatory response mainly affecting nasal mucosa. Apigenin, a flavonoid, has been documented to possess promising anti-allergic potential. Aim: To determine the potential mechanism of action of apigenin against ovalbumin (OVA)-induced AR by assessing various behavioral, biochemical, molecular, and ultrastructural modifications. Materials and Methods: Allergic rhinitis was induced in BALB/c mice (18-22 grams) by sensitizing it with OVA (5%, 500 μL, intraperitoneal [IP] on each consecutive day, for 13 days) followed by intranasal challenge with OVA (5%, 5 μL per nostril on day 21). Animals were treated with either vehicle (distilled water, 10 mg/kg, IP) or apigenin (5, 10, and 20 mg/kg, IP). Results: Intranasal challenge of OVA resulted in significant induction ( P < .05) of AR reflected by an increase in nasal symptoms (sneezing, rubbing, and discharge), which were ameliorated significantly ( P < .05) by apigenin (10 and 20 mg/kg) treatment. It also significantly inhibited ( P < .05) OVA-induced elevated serum histamine, OVA-specific IgE, total IgE, and IgG1 and β-hexosaminidase levels. Ovalbumin-induced increased levels of interleukin (IL)-4, IL-5, IL-13, and interferon (IFN)-γ in nasal lavage fluid were significantly decreased ( P < .05) by apigenin. Ovalbumin-induced alterations in splenic GATA binding protein 3 (ie, erythroid transcription factor) (GATA3), T-box protein expressed in T cells (T-bet), signal transducer and activator of transcription-6 (STAT6), suppressor of cytokine signaling 1 (SOCS1), nuclear factor-kappa B (NF-κB), and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha messenger RNA, as well as protein expressions were significantly inhibited ( P < .05) by apigenin. It also significantly ameliorated ( P < .05) nasal and spleen histopathologic and ultrastructure aberration induced by OVA. Conclusion: Apigenin regulates Th1/Th2 balance via suppression in expressions of Th2 response (IgE, histamine, ILs, GATA3, STAT6, SOCS1, and NF-κB) and activation of Th1 response (IFN-γ and T-bet) to exert its anti-allergic potential in a murine model of OVA-induced AR.

Allergic Rhinitis

1992 ◽  
Vol 13 (9) ◽  
pp. 323-328
Author(s):  
Frank S. Virant
Keyword(s):  
Allergic Rhinitis ◽  
Clinical Signs ◽  
Upper Airway ◽  
Allergic Patient ◽  
The United States ◽  
Specific Ige ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Primary Defect ◽  
Primary Focus

Epidemiology Allergic rhinitis affects as many as 8% to 10% of children in the United States. Many of these children suffer significant morbidity, leading to millions of lost school days annually. Morbidity is amplified when these children concurrently suffer from complications of allergic rhinitis, such as recurrent otitis media or chronic sinus disease. Typically, children who have allergic rhinitis have a family history of atopic disorders. Upper airway allergy may become manifest at any age, but the appearance of symptoms is most common during childhood or young adulthood. Clinical signs of rhinitis may be perennial, seasonal, or episodic, and the primary focus of complaints may relate to secondary problems, including ear, sinus, or lung disease. Pathophysiology In the allergic patient, disease is mediated by the production of antigenspecific IgE by the patient's B lymphocytes. Current research suggests that the primary defect may be the excessive production of interleukin 4 (IL-4) or a deficient level of gamma interferon (γ-INF) when a T-cell is presented with an antigen. This constellation of immunomodulators directs the B-cell to produce IgE rather than the IgG response of the non-allergic patient. Clinical disease occurs when an allergen reacts with antigen-specific IgE on the patient's nasal mast cells. When these factors combine, the mast cell is activated to release a variety of preformed and newly produced mediators, including histamine, leukotrienes, and prostaglandins (Fig 1).

Paeonol attenuates airway inflammation and hyperresponsiveness in a murine model of ovalbumin-induced asthma

2010 ◽  
Vol 88 (10) ◽  
pp. 1010-1016 ◽  
Author(s):  
Qiang Du ◽  
Gan-Zhu Feng ◽  
Li Shen ◽  
Jin Cui ◽  
Jian-Kang Cai
Keyword(s):  
Bronchoalveolar Lavage ◽  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Immunoglobulin E ◽  
Therapeutic Potential ◽  
Lavage Fluid ◽  
Interleukin 4 ◽  
Moutan Cortex ◽  
Ifn Γ ◽  
Anti Inflammatory

Paeonol, the main active component isolated from Moutan Cortex, possesses extensive pharmacological activities such as anti-inflammatory, anti-allergic, and immunoregulatory effects. In the present study, we examined the effects of paeonol on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice sensitized and challenged with ovalbumin were administered paeonol intragastrically at a dose of 100 mg/kg daily. Paeonol significantly suppressed ovalbumin-induced airway hyperresponsiveness to acetylcholine chloride. Paeonol administration significantly inhibited the total inflammatory cell and eosinophil count in bronchoalveolar lavage fluid. Treatment with paeonol significantly enhanced IFN-γ levels and decreased interleukin-4 and interleukin-13 levels in bronchoalveolar lavage fluid and total immunoglobulin E levels in serum. Histological examination of lung tissue demonstrated that paeonol significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. These data suggest that paeonol exhibits anti-inflammatory activity in allergic mice and may possess new therapeutic potential for the treatment of allergic bronchial asthma.

LncRNA MIAT Promotes Allergic Inflammation and Symptoms by Targeting MiR-10b-5p in Allergic Rhinitis Mice

2021 ◽  
Vol 35 (6) ◽  
pp. 781-789
Author(s):  
Zhiqi Ma ◽  
Haijuan Lian ◽  
Xiaoyan Lin ◽  
Yong Li
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Th17 Cells ◽  
Immunoglobulin E ◽  
Allergic Inflammation ◽  
Specific Ige ◽  
Luciferase Reporter ◽  
Mice Model ◽  
Ige Response ◽  
The Relationship

Background Allergic rhinitis (AR) is one of the most common noninfectious respiratory diseases caused by immunoglobulin E (IgE) response. Objective The study sought to explore the relationship between lncRNA MIAT and miR-10b-5p and their interaction in the regulation of allergic phenotypes in allergic rhinitis (AR) mice. Methods A mice model of AR was constructed using ovalbumin (OVA) sensitization. AR mice were treated with miR-10b-5p agomiR and LNA mediated lncRNA MIAT. The targeting relationship between MIAT and miR-10b-5p was analyzed by the ENCORI website and dual-luciferase reporter assay. The numbers of rubbing and sneezing of mice were counted. Hematoxylin-eosin (HE) staining visualized the eosinophils infiltration in nasal mucosa tissues of mice. The percentage of Th17 cells was quantitated by flow cytometry analysis. ELISA was used to detect the levels of serum OVA-specific IgE, the Th12 cytokine IL-4, and inflammatory cytokines (IL-6, IL-17). Results MIAT was up-regulated in the nasal mucosa of AR mice, while miR-10b-5p was down-regulated. MIAT directly suppressed miR-10b-5p expression in AR mice. The numbers of rubbing and sneezing, the percentage of Th17 cells, and the levels of OVA-specific IgE, IL-4, IL-6, and IL-17 in AR mice were decreased by miR-10b-5p overexpression, which was reversed by MIAT overexpression. The eosinophils infiltration in AR mice was inhibited by miR-10b-5p overexpression, which was also reversed by MIAT overexpression. Conclusion The present study demonstrates that MIAT overexpression Promotes allergic inflammation and symptoms by activating Th17 immune response via miR-10b-5p inhibition.

scholarly journals Immunomodulatory and anti-inflammatory effects of hydro-ethanolic extract of Ocimum basilicum leaves and its effect on lung pathological changes in an ovalbumin-induced rat model of asthma

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Naima Eftekhar ◽  
Ali Moghimi ◽  
Nema Mohammadian Roshan ◽  
Saeideh Saadat ◽  
Mohammad Hossein Boskabady
Keyword(s):  
Immunoglobulin E ◽  
Ethanolic Extract ◽  
Ocimum Basilicum ◽  
Interleukin 4 ◽  
Upper Respiratory Tract ◽  
Pathological Changes ◽  
Ocimum Species ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Tract Infections

Abstract Background Ocimum species (Lamiaceae) has been traditionally used for treatment of upper respiratory tract infections, bronchitis, coughs, sore throat, and wound healing. The Immunomodulatory and anti-inflammatory effects of hydro-ethanolic extract of Ocimum basilicum (O. basilicum) leaves was examined in ovalbumin sensitized animals. Methods Wistar rats were divided to six groups; non-sensitized, sensitized to ovalbumin, sensitized and treated with dexamethasone (1.25 μg/mL), and O. basilicum extract (0.75, 1.50 and 3.00 mg/mL) in drinking water for 21 days. The levels of interleukin 4 (IL-4), interferon gamma (IFN-γ), IFN-γ/IL-4 ratio, immunoglobulin E (IgE), phospholipase A2 (PLA2) and total protein (TP) in BALF, and lung pathological changes were examined. Results A significant increase in IL-4, IgE, PLA2 and TP levels, all lung pathological indices as well as significant decrease in IFN-γ/IL-4 ratio was seen in the asthmatic compared to the control rats (P < 0.05 to P < 0.001). Treatment with O. basilicum extract resulted in decreased IL-4, IgE, PLA2 and TP levels, but increased IFN-γ/IL-4 ratio compared to untreated sensitized rats (P < 0.01 to P < 0.001). The plant significantly improved the pathological changes of sensitized rats (P < 0.05 to P < 0.01). The improvement effects of higher concentrations of the O. basilicum extract were significantly more than those of dexamethasone (P < 0.05 to P < 0.001). Conclusion The improvement effects of O. basilicum on pathological changes, immunological and inflammatory markers in sensitized rats comparable or even more potent than dexamethasone suggests the therapeutic potential of the plant in asthma.

Combined Treatment With H1 and H4 Receptor Antagonists Improves Th2 Inflammatory Responses in the Nasal Mucosa of Allergic Rhinitis Rats

2021 ◽  
pp. 194589242110026
Author(s):  
Weiwei Wang ◽  
Hongwei Yu ◽  
Yongliang Pan ◽  
Shengwen Shao
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Inflammatory Responses ◽  
Combined Treatment ◽  
Interleukin 4 ◽  
Therapeutic Effects ◽  
Th2 Cytokines ◽  
Receptor Antagonists ◽  
Mhc Ii ◽  
H4 Receptor

Background Histamine H1 receptor (H1R) antagonists are the first-line drugs for the treatment of allergic rhinitis (AR) at present. Emerging evidence supports an important role of histamine H4 receptor (H4R) in allergic diseases. However, information regarding the effects of combined treatment with H1 and H4 receptor antagonists in AR is limited. Objectives We aimed to assess the effects of combined treatment with H1R and H4R antagonists on Th2 inflammatory responses in the nasal mucosa of AR rats. Methods Sprague Dawley rats were sensitized with ovalbumin and treated with H1R antagonist desloratadine or/and H4R antagonist JNJ7777120. Western blotting was used to assay the phenotypic markers of mature dendritic cells in the nasal mucosa, including major histocompatibility complex class II (MHC-II) and co-stimulatory molecules CD80, CD86 and OX40 ligand (OX40L). Th2 inflammatory cytokines including interleukin-4, 5 and 13 in nasal lavage fluids were determined by using enzyme-linked immunoassay. Results The treatment with desloratadine alone down-regulated the CD86 expression, and decreased the production of Th2 cytokines, but had no impact on the expression of MHC-II, CD80 and OX40L. The administration of NJ7777120 alone reduced the levels of CD86, OX40L and Th2 cytokines, whereas MHC-II and CD80 expression was unaffected. The combination of desloratadine and JNJ7777120 showed more significant synergistic therapeutic effects than monotherapy. Conclusion H4R antagonist acted synergistically with H1R antagonist to reduce Th2 inflammatory responses by down-regulating CD86 and OX40L expression in the nasal mucosa of AR rats. The combination with H1R and H4R antagonists might be a new strategy for AR treatment.

scholarly journals Modulation of the Gut Microbiota by Sihocheonggan-Tang Shapes the Immune Responses of Atopic Dermatitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jaemoo Chun ◽  
So Min Lee ◽  
You Mee Ahn ◽  
Min-Gyung Baek ◽  
Hana Yi ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Immunoglobulin E ◽  
Therapeutic Potential ◽  
Interleukin 4 ◽  
Hacat Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex immune dysregulation and closely related to the gut microbiome. The present study investigated the microbiome-mediated effect of Sihocheonggan-Tang (SHCGT) on AD-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice. DNCB was applied regularly to the ear and dorsal skin of BALB/c mice, and SHCGT was administered orally daily for 2 weeks. The composition of the gut microbiota was analyzed using 16S rRNA sequencing, and the effect of gut microbiome-derived metabolites, specifically short-chain fatty acids (SCFAs), was evaluated in tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-treated HaCaT cells. SHCGT alleviated DNCB-induced symptoms of AD and the immune response to AD by decreasing the plasma immunoglobulin E level and splenic interleukin-4, interleukin-10, TNF-α, and IFN-γ levels. The gut microbiome composition and the damaged gut epithelial barrier in mice with AD were also significantly altered by SHCGT, and the reduced SCFA levels therein were elevated. We found that SFCAs directly inhibited the mRNA expression of IL-6 and ICAM-1 in TNF-α- and INF-γ-treated HaCaT cells. The finding that SHCGT regulates the gut microbiome and improves DNCB-induced AD in mice suggests that this herbal medicine has therapeutic potential in patients with AD.

Arguments in favor of the use of modern blockers of H1-histamine receptors for the treatment of patients with allergic rhinitis occurring against the background of acute respiratory viral infection

2021 ◽  
Vol 20 (6) ◽  
pp. 125-135
Author(s):  
A. Yu. Ovchinnikov ◽  
◽  
N. A. Miroshnichenko ◽  
Yu. O. Nikolaeva ◽  
◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Viral Infections ◽  
Adult Population ◽  
Allergic Diseases ◽  
Therapeutic Effects ◽  
Upper Respiratory Tract ◽  
Therapy Regimen ◽  
Nasal Symptoms ◽  
Respiratory Viral Infections

Allergic rhinitis is characterized by a significant prevalence among the adult population. Patients with allergic diseases have a higher sensitivity to pathogens of acute respiratory infection of the upper respiratory tract (ARVI). Inflammation of the mucous membrane of the nasal cavity and paranasal sinuses in such patients is characterized by more pronounced symptoms and greater resistance to therapy. An observational study was conducted at the Department of Otorhinolaryngology of the Moscow State Medical University named after A. I. Evdokimov, during which the effect of modern antihistamines on the severity of nasal and non-nasal symptoms of inflammation was evaluated in patients who were diagnosed with the development of acute respiratory viral infections against the background of seasonal exacerbation of allergic rhinitis. The data of 50 patients divided into two groups were analyzed. In the first group (n = 25), benzhydrylpiperazinylbutylmethylxanthine succinate (Theoritin) was included in the therapy regimen, in the second – cetirizine preparations (n = 5). During the follow-up, each patient underwent a clinical assessment of the severity of nasal and non-nasal symptoms three times (1st, 7th and 14th days of follow-up), and the severity of nasal obstruction was assessed using anterior active rhinomanometry. According to the data obtained, there was a pronounced positive dynamics in both groups, while the clinical efficacy was confirmed by instrumental evaluation data. However, by the 7th day of treatment, the positive dynamics was more pronounced in the group of patients receiving theoritin as part of therapy. The use of modern antihistamines in patients comorbid for allergic rhinitis and acute respiratory diseases has a significant therapeutic effect. Theoritin provides more pronounced therapeutic effects in the early stages, which makes its further study and use of the drug for the treatment of acute respiratory viral infections against the background of allergic rhinitis promising.

scholarly journals Induction of interleukin 4 (IL-4) expression in T helper (Th) cells is not dependent on IL-4 from non-Th cells.

1994 ◽  
Vol 179 (4) ◽  
pp. 1349-1353 ◽  
Author(s):  
J Schmitz ◽  
A Thiel ◽  
R Kühn ◽  
K Rajewsky ◽  
W Müller ◽  
...  
Keyword(s):  
Immunoglobulin E ◽  
Specific Ige ◽  
Interleukin 4 ◽  
T Helper ◽  
Cd4 Cells ◽  
Spleen Cells ◽  
Th Cells ◽  
Ige Synthesis ◽  
Deficient Mice

Interleukin 4 (IL-4) is essential for the induction of immunoglobulin E (IgE) responses in mice. Recent in vitro studies have suggested that IL-4 derived from non T helper (Th) cells, in particular from mast cells and basophils, may be essential for triggering of IL-4 expression in Th cells and may directly contribute to IgE isotype switch induction. Here, we have generated mice carrying a functional IL-4 gene only in Th cells or non-Th cells, respectively, by reconstitution of IL-4-deficient mice (IL-4T mice) with CD4+ or CD4- spleen cells from congenic wild-type animals. In mice in which only CD4+ cells are able to express IL-4, antigen-specific IgE is produced in a T cell-dependent immune response. Thus, induction of IL-4 expression in Th cells can occur in the absence of IL-4 from non-Th cells, which suggests that at least some Th cells can express IL-4 in response to another signal which has yet to be identified. No IgE is detectable, however, in mice in which only CD4- cells can express IL-4, suggesting that Th cells are the primary, if not the only source of IL-4 for initial induction of IgE synthesis.

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