Allergic Rhinitis In Guinea Pigs Research Articles

Therapeutic potential of the topical recombinant human interleukin-1 receptor antagonist in guinea pigs with allergic rhinitis

BackgroundRecombinant human Interleukin receptor antagonist (rhIL-Ra) can bind to the IL-1 receptor on the cell membrane and reversibly blocks the proinflammatory signaling pathway. However, its effect on allergic rhinitis (AR) and the underlying mechanism remains unknown. This study aims to investigate the efficacy of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) on AR guinea pigs.MethodsGuinea pigs were systemically sensitized by intraperitoneal injection and topical intranasal instillation with ovalbumin within 21 days. Animals administrated with saline served as the normal control. The AR animals were randomly divided into the model group and distinct concentrations of rhIL-1Ra and budesonide treatment groups. IL-1β and ovalbumin specific IgE levels were detected by ELISA kits. Nasal mucosa tissues were stained with hematoxylin & eosin (HE) for histological examination.ResultsIt was found that the numbers of sneezing and nose rubbing were remarkably reduced in rhIL-1Ra and budesonide-treated guinea pigs. Besides, rhIL-1Ra distinctly alleviated IgE levels in serum and IL-1β levels in nasal mucus, together with decreased exfoliation of epithelial cells, eosinophilic infiltration, tissue edema and vascular dilatation.ConclusionsrhIL-1Ra is effective in AR guinea pigs and may provide a novel potential choice for AR treatments.

Effects of 4-DAMP on allergic rhinitis in guinea pigs and its potential mechanism.

BackgroundAllergic rhinitis (AR) is a non-infectious chronic inflammatory disease of the nasal mucosa mainly mediated by immunoglobulin E (IgE), which seriously affects the life quality of affected patients. This study aimed to observe the effects of 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; a selective M3 receptor antagonist) on ovalbumin (OVA)-induced AR guinea pigs, and to explore its potential mechanism of involvement.MethodsAn AR model was established by inducing male guinea pigs (4–6 weeks of age) with OVA. AR guinea pigs were randomly divided into a model group, 0.6 mg/kg ipratropium bromide (IB) group, 0.12 and 0.6 mg/kg 4-DAMP group (n=18). The 0.6 mg/kg IB group, 0.12 and 0.6 mg/kg 4-DAMP group animals were treated with IB (0.6 mg/kg) and 4-DAMP (0.12 or 0.6 mg/kg) by intranasal instillation per nostril daily. Animals in the model group and normal group were treated with saline as control. The AR symptom scores were counted and nasal secretion weights were measured. Histopathological methods were used to observe nasal mucosa. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of histamine and cytokines. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expressions of mucin 5AC (MUC5AC), matrix metalloproteinase 9 (MMP9), and epidermal growth factor receptor (EGFR).ResultsCompared with model group animals, the AR symptom scores and nasal secretion weights of animals treated with 4-DAMP were reduced significantly, goblet cell metaplasia was reversed, and eosinophil infiltration was visibly alleviated. The levels of histamine and cytokines in nasal lavage fluid (NLF) were decreased, and the protein and messenger RNA (mRNA) expressions of MUC5AC, MMP9, and EGFR were inhibited.ConclusionsTreatment with 4-DAMP has a certain effect on AR, especially for mucus hypersecretion, which provides a new idea for clinical treatment of AR.

Astragalus Polysaccharide Relieves Inflammatory Responses in Guinea Pigs with Allergic Rhinitis via Ameliorating NF-kB-Mediated Treg/Th17 Imbalance.

Allergic rhinitis (AR) is regarded as a prevalent and non-infectious inflammation in nasal mucosa, and astragalus polysaccharide (APS) could mitigate inflammation. Herein, this study probed the specific mechanism of APS in inflammatory responses in AR. Firstly, AR guinea pig models were established through the stimulation and sensitization of ovalbumin (OVA) and received APS treatment. Changes in nasal symptoms were assessed through counting the sneezing and rubbing times of guinea pigs. The change patterns of OVA-specific immunoglobulin-E (OVA-sIgE), OVA-specific immunoglobulin-G1 (OVA-sIgG1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in guinea pig serum were identified. Meanwhile, the levels of IL-17, transforming growth factor (TGF)-β, IL-10, and forkhead box protein P3 (Foxp3) in the guinea pig tissues or serum were examined, and CD25+Foxp3+Treg or CD4+IL17+Th17 cell proportion was detected. Afterwards, nuclear factor-kappa B (NF-kB) expression in guinea pig nasal mucosa tissues were examined. Rescue experiments were designed to probe the role of NF-kB overexpression in inflammatory responses and Treg/Th17 imbalance in AR guinea pigs. APS treatment reduced sneezing and rubbing times of AR guinea pigs and suppressed OVA-sIgE, OVA-sIgG1, TNF-α, and IL-6 levels in guinea pig serum, and meanwhile, increased CD25+Foxp3+Treg cell proportion while reduced CD4+IL17+Th17 cell proportion in AR guinea pig serum or tissues, in a dose-dependent manner. NF-kB was highly-expressed in AR guinea pigs and down-regulated after APS treatment. NF-kB overexpression facilitated inflammatory responses and Treg/Th17 imbalance in AR. APS reduced Treg/Th17 imbalance via suppressing NF-kB expression, thereby ameliorating inflammatory responses in AR.

Yiqi Jiemin decoction alleviates allergic rhinitis in a guinea pig model by suppressing inflammation, restoring Th1/Th2 balance, and improving cellular metabolism.

We investigated the mechanisms underlying the therapeutic effects of Yiqi Jiemin decoction (YJD), a traditional Chinese medicine (TCM), in the ovalbumin (OVA)-induced allergic rhinitis (AR) model in guinea pigs. YJD significantly decreased infiltration of mast cells and eosinophils into the nasal mucosa of AR model guinea pigs. YJD also increased expression of TGF-β in the nasal mucosa, restored the balance of Th1/Th2 immune cell responses, and decreased serum levels of various pro-inflammatory mediators, including histamine (HA), neuropeptide Y (NPY), acetylcholine (ACH), norepinephrine and immunoglobulin E (IgE). Metabolic analyses using liquid chromatography coupled with high-resolution mass spectrometry revealed that YJD improved cellular metabolism in AR model guinea pigs and increased serum levels of glycocholic acid while decreasing levels 1-palmitoyl lysophosphatidic acid. RNA-sequencing analysis identified BPIFB2 as a potential diagnostic biomarker and therapeutic target for AR. Functional enrichment analyses showed that YJD significantly inhibited cytokine secretion pathways in AR model guinea pigs. These findings demonstrate that YJD protects against OVA-induced AR in guinea pigs by suppressing inflammation in the nasal mucosa, restoring Th1/Th2 balance, and improving cellular metabolism.

Effect of Xingbi Gel Nasal Drops on Fyn-STAT5 Pathway in Nasal Mucosa Fibroblasts of Guinea Pigs with Allergic Rhinitis

Fyn-STAT5 is considered to be the frontier signaling pathway of IgE-mediated allergic reactions related to mast cell activation, but research on allergic rhinitis (AR) has been rarely reported. Xingbi gel nasal drops (XGND) are a compound preparation of traditional Chinese medicine, which has the exact therapeutic efficacy on AR. The current study aimed to observe the effects of XGND on Fyn-STAT5 pathway in AR guinea pig nasal mucosal fibroblasts in vitro and further illuminate the possible therapeutic mechanism of XGND on AR. The isolated and cultured nasal mucosa fibroblasts from AR guinea pigs were identified by immunocytochemical staining. Real-time PCR and western blot were performed to detect the mRNA and protein levels of the Fyn-STAT5 pathway and related cytokines in AR guinea pig nasal mucosal fibroblasts. The results indicated that XGND may interfere with the Fyn-STAT5 pathway by reducing the expression of Fyn and SCF and upregulating STAT5 and IL-10, thereby inhibiting proliferation and degranulation of mast cells, correcting Th1/Th2 immune imbalance, and then alleviating the immune response of AR fibroblasts. Our study revealed the possible regulatory mechanism of XGND in AR and laid an experimental foundation for improving the clinical efficacy of AR and enriching the clinical medication for AR.

Tussilagone inhibits allergic responses in OVA-induced allergic rhinitis guinea pigs and IgE-stimulated RBL-2H3 cells

Farfarae Flos is the dried flower buds of Tussilago farfara L. which is widely used to treat allergic and inflammatory diseases in Chinese folk. Tussilagone (TSL), a sesquiterpene compound purified from Farfarae Flos, has been confirmed the main active component in the plant. However, its anti-allergic activity hasn't been reported yet. The purpose of this study is to investigate the anti-allergic effect of TSL in ovalbumin (OVA)-induced allergic rhinitis (AR) guinea pigs and immunoglobulin E (IgE)-stimulated RBL-2H3 cells. The AR symptoms such as nasal scratching, sneezing and runny nose were scored and the histological changes of nasal mucosa were observed by H&E staining. The levels of histamine, OVA-specific IgE, IL-6 and TNF-α in the serum were measured by ELISA. In IgE-stimulated RBL-2H3 cells, the phosphoryration of Lyn, Syk, Akt, NF-κB p65, ERK and p38 MAPK were investigated by western blot analysis. The results showed that intraperitoneal injection of TSL at doses of 25 and 50 mg/kg significantly alleviated the allergic symptoms and the histological changes of nasal mucosa in OVA-induced allergic rhinitis guinea pigs. Moreover, the levels of histamine, IgE and IL-6 in the serum decreased significantly (p < .05). In vitro, TSL suppressed the phosphorylation of Lyn, Syk, Akt, NF-κB p65, ERK and p38 MAPK in IgE-stimulated RBL-2H3 cells. These results indicate TSL has therapeutic effect on allergic rhinitis in guinea pigs. The anti-allergic mechanism may be through the inhibition of allergic and inflammatory related pathways in mast cells.

Ethno-medicinal study of Artemisia ordosica Krasch. (traditional Chinese/Mongolian medicine) extracts for the treatment of allergic rhinitis and nasosinusitis.

Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.

Effect of hydrogen-rich saline on the CD4(+) CD25(+) Foxp3(+) Treg cells of allergic rhinitis guinea pigs model

Objective: To explore the effect of hydrogen-rich saline on the CD4(+) CD25(+) Foxp3(+) Treg cells in a guinea pig model of allergic rhinitis (AR) and investigate the underling anti-inflammatory mechanism. Methods: Using random number table, eighteen guinea pigs were divided into three groups (control group/AR group/HRS group, n=6 of each group). AR guinea pig model was built with ovalbumin and aluminum. The guinea pigs were injected with hydrogen-rich saline (HRS group) for ten days after sensitation. And control group was injected with equal normal saline at the same time. Number of sneezes, degree of runny nose and nasal rubbing movements were scored. Peripheral blood eosinophil count was recorded. The content of interleukin 10(IL-10) and transforming growth factor β (TGF-β) in the serum were detected by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical method was taken to detect IL-10 and TGF-β in nasal mucosa. The proportion of CD4(+) CD25(+) Foxp3(+) T cells in the CD4(+) T cells of spleen and peripheral blood were determined with flow cytometry. SPSS 17.0 software was used to analyze the data. Results: There was significant difference in symptom scores among them. The scores of AR group preceded control group, and HRS could decrease the scores of AR ((6.29±1.79) vs (1.01±0.71), (4.50±0.84) vs (6.29±1.79), F=24.725, all P<0.05). The highest number of eosinophils in the peripheral blood belonged to control group, and the number of eosinophils were dramatically reduced after HRS administration ((0.41±0.05)×10(9)/L vs (0.25±0.03 )×10(9)/L, (0.32±0.03)×10(9)/L vs (0.41±0.05)×10(9)/L, F=70.05, all P<0.05). The content of IL-10 and TGF-β in control group is peak ((86.88±17.17) pg/ml, (598.28±72.70) pg/ml, respectively), and compared with AR group, HRS also increased the expression of IL-10 and TGF-β of peripheral blood ((72.54±11.75) pg/ml vs (53.49±10.07) pg/ml, (530.23±57.15) pg/ml vs (482.69±65.96) pg/ml, F value was 28.357, 14.128, respectively, all P<0.05). The proportion of CD4(+) CD25(+) Foxp3(+) Treg cells in controls exceeded HRS group and AR group (1.81%±0.10%, 1.29%±0.74%, respectively), and HRS treatment increased the ratio of CD4(+) CD25(+) Foxp3(+) Treg cells than AR group of peripheral blood ((1.50%±0.11%) vs (1.15%±0.11%), F=168.96, P<0.05). But there was no significant diferences in splene tissue ((1.01%±0.08%) vs (0.98%±0.09%), F=97.381, P>0.05). Conclusion: Both the number and the cytokine secretion of CD4(+) CD25(+) Foxp3(+) Treg cells are decreased in AR group, HRS may inhibit inflammatory response and ameliorate AR via improving the number and the cytokine secretion.

Changes in IL-4 and IL-13 expression in allergic-rhinitis treated with hydrogen-rich saline in guinea-pig model

BackgroundMedical gas hydrogen (H2) has a special role in airway inflammation; however, the effect of H2 on allergic rhinitis (AR) remains unclear. This study explored the possible roles of H2 on the pathogenesis of AR and observed the influences of H2 on cytokines IL-4 and IL-13. MethodsAn AR guinea pig model was established by nasal ovalbumin sensitisation. Eighteen guinea pigs were divided into three groups, namely, saline control, AR-sensitised, and hydrogen-rich saline (HRS)-treated groups, with each group having six guinea pigs. The frequencies of sneezing and scratching were recorded. The IgE level and cytokine (IL-4 and IL-13) levels in the serum were measured. The expression levels of IL-4 and IL-13 mRNA and protein in the nasal mucosa were also determined by real-time reverse transcriptase–polymerase chain reaction and Western blot. We also observed the infiltration of cytokine (IL-4 and IL-13) in nasal mucosa by immunofluorescence. ResultsThe frequencies of sneezing and scratching, as well as the levels of IgE, IL-4, and IL-13, in the serum were higher in the AR group than in the control group (p<0.01), whereas all these parameters were decreased significantly after HRS treatment (p<0.05). The expression levels of IL-4 and IL-13 mRNA and protein in the nasal mucosa were also lower in guinea pigs treated with HRS than those in the AR group (p<0.05). ConclusionsHRS could affect anti-inflammation in AR and decreased the expression of IL-4 and IL-13.

Inhibitory effect of baicalin on allergic response in ovalbumin-induced allergic rhinitis guinea pigs and lipopolysaccharide-stimulated human mast cells.

Baicalin, a flavonoid compound purified from the dry roots of Scutellaria baicalensis Georgi, has generally been used for the treatment of various allergic diseases. However, there is little information about the anti-inflammatory effects of baicalin for allergic rhinitis. This study aims to investigate the anti-allergic effect of baicalin on allergic response in ovalbumin (OVA)-induced allergic rhinitis guinea pigs and lipopolysaccharide (LPS)-stimulated human mast cells. Using in vivo models, we evaluated the effect of baicalin on allergic rhinitis symptoms via recording the number of nasal rubs and sneezes. The levels of histamine, OVA-specific immunoglobulin E(IgE), eosinophil cationic protein (ECP) and inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The histological changes of nasal mucosa were observed by light microscope after HE staining. In vitro, the release of histamine and β-hexosaminidase of compound 48/80-induced human mast cells were measured by ELISA and PNP-NAG colorimetry, respectively. The productions of inflammatory cytokines of LPS-stimulated human mast cells were determined using ELISA. Western blot was used to test the protein expression of JAK2, p-JAK2, STAT5, p-STAT5, IKKβ, p-IKKβ, IκBα, p-IκBα and NF-κB (p65) of LPS-stimulated human mast cells. The oral administration of baicalin at doses of 50 and 200mg/kg improved allergic rhinitis symptoms and the histological changes of nasal mucosa and decreased the serum levels of histamine, ECP, interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α and OVA-specific IgE in OVA-induced allergic rhinitis guinea pigs. In vitro, baicalin suppressed the release of histamine and β-hexosaminidase in compound 48/80-induced human mast cells. In addition, baicalin also inhibited the productions of inflammatory cytokines such as IL-1β, IL-6, IL-8 and TNF-α and suppressed the phosphorylation of JAK2, STAT5, IKKβ, IκBα and the nuclear translocation of NF-κB (p65) subunit in LPS-stimulated human mast cells. These results suggest that baicalin can effectively prevent allergic response in OVA-induced allergic rhinitis guinea pigs and inhibit inflammatory response via blocking JAK2-STAT5 and NF-κB signaling pathways in LPS-stimulated human mast cells. Considered together,the results show that baicalin may be a useful drug in the treatment of allergic rhinitis.

Prostaglandin D2 Modulates Neuronal Excitation of the Trigeminal Ganglion to Augment Allergic Rhinitis in Guinea Pigs.

Prostaglandin D2(PGD2) is involved in the pathogenesis of allergic rhinitis. However, the sensory nervous system-mediated contributions of PGD2to the symptoms of allergic rhinitis remain unclear. We investigated the involvement of PGD2in these symptoms and in neuronal excitation by in vivo and ex vivo experiments. In an ovalbumin-induced model of allergic rhinitis in guinea pigs, the number of sneezing, nasal rubbing, and nasal secretion events were assessed after the nasal cavity instillation of PGD2, histamine, or a combination of PGD2and histamine. In situ hybridization for PGD2receptor 1 (DP1) mRNA transcripts and immunohistochemical analysis of histamine H1receptor protein expression in guinea pig trigeminal ganglion (TRG) were performed. The effects of DP1receptor activation on the excitability of TRG neurons to electrical and histamine stimuli were assessed using whole-cell patch-clamp recordings. Histamine induced more sneezing, nasal rubbing, and nasal secretion events than PGD2 PGD2augmented histamine-induced responses, whereas pretreatment with a DP1receptor-selective antagonist completely suppressed PGD2-induced augmentation. DP1receptor mRNA transcripts and H1receptor protein expression could be detected in TRG neurons. Moreover, a DP1receptor agonist caused significant increases in the number of histamine-induced action potentials and depolarization, and reduced the current threshold in small-diameter neurons. Our findings show that PGD2-DP1receptor signaling augments the symptoms of allergic rhinitis via the sensory nervous system by modulating nasal neuronal activation to various stimuli, such as histamine. These findings suggest that DP1receptor antagonist has therapeutic potential for the treatment of allergic rhinitis.

Anti-Interleukin-1 Beta/Tumor Necrosis Factor-Alpha IgY Antibodies Reduce Pathological Allergic Responses in Guinea Pigs with Allergic Rhinitis.

This study aims to determine whether the combined blockade of IL-1β and TNF-α can alleviate the pathological allergic inflammatory reaction in the nasal mucosa and lung tissues in allergic rhinitis (AR) guinea pigs. Healthy guinea pigs treated with saline were used as the healthy controls. The AR guinea pigs were randomly divided into (1) the AR model group treated with intranasal saline; (2) the 0.1% nonspecific IgY treatment group; (3) the 0.1% anti-TNF-α IgY treatment group; (4) the 0.1% anti-IL-1β IgY treatment group; (5) the 0.1% combined anti-IL-1β and TNF-α IgY treatment group; and (6) the fluticasone propionate treatment group. The inflammatory cells were evaluated using Wright's staining. Histopathology was examined using hematoxylin-eosin staining. The results showed that the number of eosinophils was significantly decreased in the peripheral blood, nasal lavage fluid, and bronchoalveolar lavage fluid (P < 0.05), and eosinophil, neutrophil, and lymphocyte infiltration and edema were significantly reduced or absent in the nasal mucosa and lung tissues (P < 0.05) in the combined 0.1% anti-IL-1β- and TNF-α IgY-treated guinea pigs. The data suggest that topical blockade of IL-1β and TNF-α could reduce pathological allergic inflammation in the nasal mucosa and lung tissues in AR guinea pigs.

Longitudinal study of effects of oral dosage of Bifidobacterium bifidum G9-1 on Japanese cedar pollen-induced allergic nasal symptoms in guinea pigs.

Previous studies using experimental animal models have reported the beneficial effects of probiotics on allergic responses; however, their long-term effects on allergic nasal symptoms in clinical settings have not yet been elucidated in detail. In the present study, a guinea pig allergic rhinitis model involving repeated inhalation challenges with a natural allergen, Japanese cedar pollen, was used to examine the longitudinal effects of Bifidobacterium bifidum G9-1 (BBG9-1) on allergic nasal symptoms. BBG9-1 was administered orally once a day. Amelioration of nasal blockage was consistently observed throughout the experimental period in the BBG9-1-treated group. Although challenge-induced sneezing was not significantly inhibited in the BBG9-1-treated group, prolonged treatment with BBG9-1 slightly reduced the frequency of sneezing. Antigen-specific IgE antibody production was also not inhibited in the BBG9-1-treated group. Increases in the numbers of eosinophils and neutrophils in nasal cavity lavage fluid collected after pollen challenge were almost completely suppressed by BBG9-1 treatment, whereas those in mast cell mediators, histamine and cysteinyl leukotrienes were not. In contrast, increases in the levels of nitric oxide metabolites were potently suppressed. Furthermore, prolonged BBG9-1 treatment markedly suppressed exogenous leukotriene D4 -induced nasal blockage. Thus, prolonged oral administration of BBG9-1 suppresses Japanese cedar pollen-induced allergic nasal symptoms. The inhibitory mechanisms responsible may involve reductions in the responsiveness of target organs, such as endothelial cells in nasal mucosal blood vessels, to chemical mediators.

Desloratadine citrate disodium injection, a potent histamine H1 receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades

Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway.

Effects of Xingbi gel on leukotriene E4 and immunoglobulin E production and nasal eosinophilia in a guinea pig model for allergic rhinitis.

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal airways.Many therapies do not have immediate effects,even which have side-effects.However,the effects of Xingbi gel for the treatment of AR was investigated. We investigated the effects of Xingbi gel on serum levels of leukotriene E4 (LTE4) and immunoglobulin E (IgE), as well as eosinophil counts in the nasal mucosa using a guinea pig model of allergic rhinitis (AR). In addition to a healthy control group without AR, guinea pigs with AR were randomly divided into untreated AR control group, low-dose Xingbi gel (0.2483 g/mL) group, high-dose Xingbi gel (0.4966 g/mL) group, and budesonide group. Compared to the healthy controls, untreated AR guinea pigs had significantly higher ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts (p <0.01). Treatments with low-dose Xingbi gel, high-dose Xingbi gel, and budesonide significantly reduced the ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts as compared to untreated AR model guinea pigs (p <0.01). Xingbi gel alleviates AR in part through inhibiting LTE4 and IgE production and reducing eosinophilia in the nasal mucosa.

Establishment of a new animal model of allergic rhinitis with biphasic sneezing by intranasal sensitization with Staphylococcal enterotoxin B.

Allergic rhinitis (AR) is a global health problem. The effectiveness of currently available medications is limited and therefore investigation for more effective drugs is essential. The aim of the present study was to establish a model of AR in guinea pigs that can be utilized for the further investigation of new drugs. Guinea pigs were intranasally sensitized with 1 µg Staphylococcal enterotoxin B (SEB) dissolved in 40 µl saline once daily for 14 days. One week after the last sensitization, the same treatment was applied intranasally once every four days for a total of 30 times. In the treatment group, terfenadine was administered orally 70 min before the 4th, 14th and 24th challenge. Sneezing and nasal scratching were evaluated following each of the 30 challenges. The quantity of antigen-specific antibodies in the serum was measured. Between the 19th and 30th challenges, the guinea pigs in the model group produced significant biphasic elevations in sneezing number, with peaks 10 min-2 h and 4-8 h after the SEB challenges. In addition, the guinea pigs produced significantly more sneezing in the first peak during the 19th to 30th challenges than during the first to 18th challenges (P<0.01). Terfenadine significantly inhibited the early- and late-phase sneezing at all challenge times. The serum levels of SEB-specific immunoglobulin (Ig) E and IgG1 were higher in the model group in comparison with those in the control group (P<0.01). This experiment demonstrated that SEB can induce typical AR with biphasic sneezing in guinea pigs. Histamine may play an important role in the early- and the late-phase sneezing in the model of AR. This model can be potentially used for the investigation of new drugs.

Impact of carbon monoxide/heme oxygenase on hydrogen sulfide/cystathionine-γ-lyase pathway in the pathogenesis of allergic rhinitis in guinea pigs.

The discovery of carbon monoxide (CO) and hydrogen sulfide (H2S) as pathogenic signaling molecules in airway-related diseases has led to significant insights into the pathophysiologic mechanisms underlying the development of allergic rhinitis (AR). The potential crosstalk between CO and H2S signaling pathways in AR has not been adequately investigated. This study was performed to elucidate the mechanistic relationship between CO and H2S in AR. Experimental prospective animal study. Animal laboratory of Tongji Hospital, Tongji University, Shanghai, China. A well-established model of AR was used whereby guinea pigs (N=24) were randomly divided into 4 treatment groups (n=6 for each group): The first group received ovalbumin only; the second group was administered exogenous hemin, a CO-binding metalloporphyrin; the third group received zinc protoporphyrin, an inhibitor of heme oxygenase-1. A control group was challenged using only saline. Symptoms of AR were recorded, and quantitation of plasma CO and H2S levels was performed. Expression of heme oxygenase-1 and H2S-generating enzyme cystathionine-γ-lyase (CSE) were measured from nasal mucosa. Plasma CO and heme oxygenase-1 expression levels of nasal mucosa were significantly increased in the AR group compared to controls, whereas H2S concentrations were significantly decreased. Exogenous administration of CO exacerbated allergic symptoms, resulting in higher levels of both CO and heme oxygenase-1 expression, and a further reduction in H2S levels and CSE expression. Zinc protoporphyrin decreased CO concentrations and increased levels of both H2S and CSE expression. Results indicated an inverse relationship between H2S levels and CO in the pathogenesis of AR.

Therapeutic potential of combined anti-IL-1β IgY and anti-TNF-α IgY in guinea pigs with allergic rhinitis induced by ovalbumin.

We have previously demonstrated that anti-IL-1β immunoglobulin yolk(IgY) inhibits pathological responses in allergic asthma guinea pigs induced by ovalbumin(OVA). This study aims to determine whether the combined blockade of IL-1β and TNF-α can more effectively inhibit allergic inflammation in allergic rhinitis(AR) guinea pigs induced by OVA. Healthy guinea pigs treated with saline were used as the healthy control. The AR guinea pigs induced by OVA were randomly divided into (1) the AR model group containing negative control animals treated with intranasal saline; (2) the 0.1% non-specific IgY treatment group treated with non-specific IgY; (3) the 0.1% anti-TNF-α IgY treatment group treated with 0.1% anti-TNF-α IgY; (4) the 0.1% anti-IL-1β IgY treatment group treated with 0.1% anti-IL-1β IgY; (5) the 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY treatment group treated with 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY; and (6) the fluticasone propionate treatment group treated with fluticasone propionate. Cytokines were measured using an enzyme-linked immunosorbent assay. The results showed that IL-1β, IL-5, IL-9, IL-13, IL-18, IL-22, IL-33, TNF-α, TGF-β1 and OVA-specific IgE levels in the peripheral blood (PB) and nasal lavage fluid (NLF) significantly decreased at 2h, 4h or 8h in the 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY treatment group compared to the AR model group and the 0.1% non-specific IgY treatment group (P<0.05). The data suggest that blockade of IL-1β and TNF-α by intranasal instillation of combined anti-IL-1β IgY and anti-TNF-α IgY could be a potential alternative strategy for preventing and treating allergic rhinitis.

Therapeutic potential of curcumin in experimentally induced allergic rhinitis in guinea pigs

In the present experiments, the possible role of curcumin in ovalbumin induced allergic rhinitis in guinea pig model was investigated. Various allergic rhinitis symptoms viz sneezing, rubbing frequencies, lacrimation and nasal congestion at various humidity conditions as well as on repeated sensitization were studied. The biochemical changes like serum IgE, IL-4 and nitric oxide (NO) in nasal lavage and eosinophil peroxidase activity in nasal homogenates were determined in allergic rhinitis. Curcumin treatment significantly reduced the symptoms (sneezing, rubbing frequencies, lacrimation and nasal congestion) and improved the histopathological alterations (reduction in inflammatory cells infiltration) of nasal mucosa in allergic rhinitis. Furthermore, curcumin treatment prevented significantly elevation of serum IgE, IL-4, NO in nasal lavage and eosinophil peroxidase in nasal homogenate. In the present experimental findings, we suggest that curcumin is a promising anti-allergic agent that may be useful in the clinical management of allergic rhinitis.

Effect of KOB03, a polyherbal medicine, on ovalbumin-induced allergic rhinitis in guinea pigs

BackgroundKOB03 is a polyherbal medicine that originated from the oriental prescription for the treatment of chronic allergic diseases such as rhinitis and asthma. This study aims to evaluate the effect of KOB03 on ovalbumin (OVA)-induced allergic rhinitis (AR) in guinea pigs.MethodsHartley guinea pigs were sensitized to OVA by intraperitoneal injection on days 0, 7, and 14 and challenged with intranasal exposure to OVA three times for 7 days after the last sensitization. KOB03 at doses of 200 and 500 mg/kg were orally administrated to guinea pigs once daily during challenge. The serum levels of histamine, OVA-specific immunoglobulin (Ig) E, eosinophil cationic protein (ECP) and cytokines (TNF-α, IL-4 and IFN-γ) in OVA sensitization/challenge-induced AR guinea pigs were measured. We also observed histological changes in nasal tissues of AR guinea pigs by staining with H&E, Periodic acid-Schiff, and toluidine blue.ResultsThe administration of KOB03 at a dose of 500 mg/kg significantly decreased the serum levels of histamine (P = 0.001), OVA-specific IgE (P = 0.0017), ECP (P = 0.008), and TNF-α (P = 0.0003) in OVA-sensitized/challenged guinea pigs compared with controls. KOB03 significantly decreased the serum levels of a Th2 cytokine, IL-4 (P = 0.017), while significantly increasing the levels of a Th1 cytokine, IFN-γ (P = 0.0006) in OVA-sensitized/challenged guinea pigs compared with controls. In addition, KOB03 suppressed the epithelial destruction, goblet cell hyperplasia and eosinophilic infiltration into nasal mucosa associated with AR.ConclusionKOB03 may regulate allergic inflammation in AR by inhibiting nasal damage, the release of allergic mediators and modulating the balance of Th1/Th2 cytokines.