Pollen Inhalation Research Articles

Effect of Local Nasal Immunotherapy on Nasal Blockage in Pollen-Induced Allergic Rhinitis of Guinea Pigs

As a non-injection route for immunotherapy, local nasal immunotherapy has been examined in allergic rhinitis patients. However, it is unclear how the immunotherapy affects sneezing, biphasic nasal blockage and nasal hyperresponsiveness. Thus, we evaluated the therapeutic effects of nasal immunotherapy on the symptoms of guinea pig allergic rhinitis. Additionally, we also evaluated whether the immunotherapy relieved pollen-induced allergic conjunctivitis. Sensitized animals were repeatedly challenged by pollen inhalation once every week. After the 7th challenge, the pollen extract was intranasally administered 6 times a week until the 30th challenge. Sneezing frequency was counted after each of the challenges. As an indicator of nasal blockage, changes in specific airway resistance were measured. Nasal hyperresponsiveness was assessed by measuring leukotriene D(4)-induced nasal blockage. Additionally, during the immunotherapy, we applied pollen onto the ocular surface to induce the allergic conjunctivitis symptoms. At the 11th-30th challenges, the nasal immunotherapy showed inhibition or a tendency to inhibit the biphasic nasal blockage although the inhibitions were variable at respective challenges. The development of nasal hyperresponsiveness was markedly suppressed by the immunotherapy. Nevertheless, neither sneezing nor antigen-specific IgE antibody production was substantially influenced by the immunotherapy. On the other hand, the nasal immunotherapy did not affect the induction of allergic conjunctivitis symptoms. Local nasal immunotherapy may be clinically useful for allergic nasal blockage associated with nasal hyperresponsiveness. The mechanisms responsible for this effectiveness might not be related to IgE production. Additionally, the effectiveness for nasal tissue was dissociated from that seen for the ocular tissue.

Involvement of peroxynitrite in pollen-induced nasal blockage in guinea pigs

Nitric oxide (NO) has been implicated in early and late phase nasal blockage in a Japanese cedar pollen-induced experimental allergic rhinitis guinea pig model. In this study, we investigated the role of peroxynitrite, which is formed by a rapid reaction of NO with superoxide anion, in the antigen-induced biphasic nasal blockage. Sensitized guinea pigs were repeatedly challenged by pollen inhalation once every week. The peroxynitrite scavenger, ebselen (30 mg/kg), or the xanthine oxidase inhibitor, allopurinol (50 mg/kg), was intraperitoneally administered 30 min before the antigen challenge. The late phase nasal blockage induced 4 h after the challenge was largely suppressed by ebselen (57% inhibition; P < 0.05) and allopurinol (47% inhibition; P < 0.05), but neither ebselen nor allopurinol influenced the early phase response. On the other hand, the intranasal instillation of peroxynitrite (10 − 3 and 10 − 2 M, 10 μl/nostril) caused a remarkable dose-dependent nasal blockage in the sensitized guinea pig. These results suggest that peroxynitrite plays a major role in the late phase nasal blockage induced by the antigen challenge in sensitized guinea pigs.

Effect of Oral Immunotherapy on Nasal Blockage in Experimental Allergic Rhinitis

We previously reported that when Japanese cedar pollen was prophylactically p.o. administered before a sensitization stage in a guinea-pig model of allergic rhinitis, pollen-induced nasal blockage was suppressed. In this study, we evaluated whether the oral immunotherapy is also effective when the pollen extract was administered starting from the day when the nasal blockage was clearly induced and whether the effectiveness continued after cessation of the immunotherapy. Sensitized animals were repeatedly challenged by pollen inhalation once every week. After the 7th challenge, the extract was orally administered twice a week until the 30th challenge. At the 11th challenge, the oral immunotherapy showed inhibition of the biphasic nasal blockage. The effectiveness was consistently observed during the immunotherapy until the 30th challenge. Furthermore, the increased nasal responsiveness to intranasal application of leukotriene D4 was markedly suppressed by the immunotherapy. Interestingly, even after cessation of the therapy, inhibition of the nasal blockage was sustained for more than 2 months. Nevertheless, neither sneezing nor antigen-specific IgE antibody production was substantially influenced by the immunotherapy. In conclusion, Oral immunotherapy may be clinically useful for allergic nasal blockage. Mechanisms underlying the effectiveness may be associated with the hyporesponsiveness of the nasal mucosa to released mediators.

Synergism between cysteinyl leukotrienes and thromboxane A 2 to induce allergic late phase nasal blockage in guinea pigs

We examined whether cysteinyl leukotrienes (CysLTs) and thromboxane (TX) A 2 are synergistically involved in a cedar pollen-induced allergic late phase nasal blockage in guinea pigs. Sensitized animals were repeatedly challenged by pollen inhalation once every week. Combined treatment with pranlukast (a CysLT antagonist) and seratrodast (a TXA 2 antagonist) inhibited late phase nasal blockage, but the magnitude of inhibition (approximately 50%) was equal to those of the respective single treatments, suggesting that CysLTs produced late after challenge induces TXA 2 production in the nasal tissue, as in the case of the lung of this species. However, pranlukast did not affect TXB 2 increase in the nasal tissue. In contrast, combined intranasal instillation of LTD 4 and U-46619 (a TXA 2 mimetic) produced much greater nasal blockage than single administration of each agonist in sensitized animals. Therefore, allergic late phase nasal blockage should be induced by synergistic activity of CysLTs and TXA 2 at the effector organ.

Preventive and curative effects of Gyokuheifu-san, a formula of traditional Chinese medicine, on allergic rhinitis induced with Japanese cedar pollens in guinea pig.

Gyokuheifu-san (GHS; Jade Windscreen Powder in English, Yupingfeng-san in Chinese) is an herbal formula in traditional Chinese medicine that consolidates the superficial resistance to protect from invasion by external pathogenic influences. We evaluated the preventive and curative effects of GHS on allergic rhinitis induced by Japanese cedar pollens in guinea pigs, since the pollen can be considered one of external pathogens indicated by GHS. Guinea pigs were sensitized by intranasal instillation of cedar pollen extract with alum twice a day for 7 d, and the animals were then forced to inhale the pollens for challenge once a week for 5 weeks. We administered GHS once a day for 2 weeks in the period of sensitization to evaluate its preventive effect, or for 2 weeks from the 2nd to the 4th week of pollen inhalation, once pollinosis had begun, to evaluate its curative effect on allergic rhinitis. GHS significantly suppressed the frequency of sneezing induced by pollens and tended to reduce nose-scratching behavior after ceasing its administration in both designs of medicinal treatment. Tranilast, which is an anti-allergic drug we used as a positive control, could not suppress these rhinitic symptoms. GHS appears to have non-symptomatic and non-allopathic effects on allergic rhinitis. Our results suggest that traditional medicines have their own characteristics different from modern medicines, and the original pharmacological experiments are important to evaluate traditional medicines scientifically.

Validation of an environmental exposure unit for controlled human inhalation studies with grass pollen in patients with seasonal allergic rhinitis.

There is an increasing need for allergen inhalation systems to perform basic clinical research and test anti-allergic drugs under well-controlled conditions. This requires stability of environmental conditions like temperature and humidity, as well as allergen concentration and reproducible induction of allergic symptoms. The aim of this study was to validate an environmental exposure unit for controlled human pollen inhalation studies in participants with seasonal allergic rhinitis. Temperature, relative humidity, and air flow rate were kept constant with an air conditioning system. Pollen atmosphere was generated using a specially designed feeding system and monitored online by laser counter and offline using rotating rod samplers. Efficacy (total nasal symptom score, nasal air flow rate, nasal secretion) and safety (lung function) parameters were evaluated at different pollen concentrations and repeated allergen challenges. Temperature, humidity, and air flow rate in the environmental exposure unit remained constant within a range of <2%. The spatial distribution and the temporal stability of the pollen concentration varied only slightly over 4 h (+/-10% and <4%, respectively). Dose-dependent induction of allergic rhinitis symptoms, reduction in nasal air flow rate, and increase in nasal secretion were observed over time. These effects were reproducible from day to day. Lung function remained clinically normal at all concentrations and from day to day. Thus, pollen exposure in the environmental exposure unit is an effective, reproducible, safe, and suitable method for single-centre clinical studies on the efficacy of anti-allergic treatment or basic clinical research.

Kinins are involved in the development of allergic nasal hyperresponsiveness in guinea pigs

We evaluated roles of kinins in allergen-induced nasal blockage and sneezing, and development of nasal hyperresponsiveness to leukotriene D 4 in a Japanese cedar pollen-induced allergic rhinitis model of guinea pigs. Sensitised guinea pigs were repeatedly challenged by pollen inhalation once every week. Neither a bradykinin B 1 receptor antagonist, des-Arg 9-[Leu 8]bradykinin nor a bradykinin B 2 receptor antagonist, icatibant suppressed allergen-induced sneezing and nasal blockage. However, development of nasal hyperresponsiveness to leukotriene D 4 was significantly suppressed by them. The amount of bradykinin in nasal cavity lavage fluid was immediately increased after the challenge. In non-sensitised animals, hyperresponsiveness to leukotriene D 4 was developed by a bradykinin B 2 receptor agonist, bradykinin, but not by a bradykinin B 1 receptor agonist, des-Arg 10-kallidin, while in the sensitised-challenged animal, both agonists developed hyperresponsiveness. In conclusion, the nasal hyperresponsiveness appeared to be induced by kinins produced in response to the antigen challenge through activation of not only bradykinin B 2 but also B 1 receptors.

Studies on the Experimental Allergic Rhinitis Induced by Japanese Cedar Pollen — Role of Cysteinyl Leukotrienes in Nasal Allergic Symptoms

AbstractFor Abstract see ChemInform Abstract in Full Text.

Studies on the experimental allergic rhinitis induced by Japanese cedar pollen--role of cysteinyl leukotrienes in nasal allergic symptoms

Cysteinyl leukotrienes (CysLTs: LTC4, LTD4, and LTE4) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of allergic rhinitis. Because treatment with a CysLT1 receptor antagonist and a 5-lipoxygenase inhibitor modified allergen-induced nasal blockage in patients with allergic rhinitis, and CysLTs were detected in nasal cavity lavage fluid, it has been suggested that CysLTs act as significant inflammatory mediators in allergic rhinitis. The role of CysLTs was evaluated in our experimental allergic rhinitis model in sensitized guinea pigs which shows biphasic nasal blockage, sneezing and nasal hyperresponsiveness to LTD4 induced by repetitive inhalation challenge with Japanese cedar pollen. In this model, the CysLT1 receptor antagonist pranlukast suppressed the late-phase nasal blockage but not early blockage and sneezing. Nasal hyperresponsiveness (nasal blockage) to LTD4 was largely blocked by pranlukast, naphazoline, and N omega-nitro-L-arginine-methyl ester. The results demonstrate that nasal blockage induced by CysLTs is mainly due to dilatation of nasal blood vessels, which can be induced by the nitric oxide produced through CysLT1 receptor activation. On the other hand, when pollen inhalation challenge was performed in the presence of nasal hyperresponsiveness, antigen-induced biphasic nasal blockage and sneezing were considerably enhanced and CysLTs contributed to both symptoms, suggesting that nasal hyperresponsiveness induces aggravation of antigen-induced nasal symptoms. The results presented in this study further suggest that our model is a good representative of human allergic rhinitis and offer evidence that CysLTs are chemical mediators mainly responsible for allergic nasal symptoms.

Pharmacological characterization of the leukocyte kinetics after intranasal antigen challenge in a guinea pig model of allergic rhinitis.

We characterized the leukocyte kinetics after antigen challenge, and investigated the effects of the thromboxane (TX) A2 antagonist seratrodast, the peptide leukotriene (p-LT) antagonist pranlukast, the antihistaminic drug terfenadine and the glucocorticoid dexamethasone on this leukocyte response in a guinea pig model of allergic rhinitis. Male Hartley guinea pigs were used. Intranasally sensitized guinea pigs were challenged once every week for 15 weeks by inhalation of Japanese cedar pollen as the antigen. Dexamethasone and other agents were administered orally 3 and 1 h, respectively, before the 15th challenge. The time-related changes in the numbers of differential leukocytes in nasal cavity lavage fluid (NCLF) and in peripheral blood after pollen inhalation challenge were investigated. The effects of the drugs on the antigen-induced changes in the leukocyte counts were evaluated. In addition, histopathological examination of the nasal mucosa was also performed 5 h after the challenge. There was a marked increase in the number of leukocytes in NCLF, especially of eosinophils, which peaked at 5 h, after antigen challenge in this model. This response was also accompanied by the peripheral blood eosinophilia and neutrophilia. Seratrodast (30 mg/kg), pranlukast (30 mg/kg) and dexamethasone (10 mg/kg) inhibited the eosinophilia in all of the blood, the nasal mucosa and NCLF seen 5 h after the antigen challenge. Terfenadine (10 mg/kg) had no apparent effect on the blood and the mucosal eosinophilia, although it tended to suppress the eosinophil accumulation in NCLF. These results suggest that the present model is useful for analyzing the mechanisms of antigen-induced eosinophilic inflammation in allergic rhinitis and that both TXA2 and p-LTs, but not histamine, contribute to the antigen-induced eosinophilia in this model of allergic rhinitis.

Comparison of Cedar Pollen-Induced Allergic Rhinitis in Passively and Actively Sensitized Guinea Pigs

We have developed an allergic rhinitis model in guinea pigs using Japanese cedar pollen as antigen. In the present study, we examined whether provocation by pollen induces similar magnitudes of rhinitis symptoms in passively and actively sensitized guinea pigs. One group of animals was actively sensitized by intranasal application of pollen extract, and another was passively sensitized by intraperitoneal injection with anti-pollen serum. Actively and passively sensitized groups were then challenged by repeated and a single pollen inhalation, respectively. In both groups, sneeze was induced immediately after the challenge. The actively sensitized animals developed not only early but also late nasal blockage, whereas the passively sensitized animals showed only early nasal blockage. In both groups, an Hi antagonist, mepyramine, inhibited the occurrence of sneezing but did not inhibit nasal blockage. Nasal hyperresponsiveness to intranasal instillation of leukotriene D4 was obvious only in the actively sensitized animals. We thus conclude that although early nasal blockage is induced by a single antigen-antibody reaction, repetitive anaphylactic reaction is required for occurrence of late nasal blockage and hyperresponsiveness to stimuli. Furthermore, his-tamine plays a central role in induction of sneezing but not in nasal blockage, irrespective of whether animals are actively or passively sensitized.

Atopy patch testing--a diagnostic tool?

Atopy patch testing--a diagnostic tool?

Development of pollen-induced allergic rhinitis with early and late phase nasal blockage in guinea pigs.

Development of nasal blockage and sneezing during repeated inhalation challenges with Japanese cedar pollens was evaluated in guinea pigs. Male Hartley guinea pigs. Guinea pigs were sensitized by intranasal instillation of cedar pollen extracts + Al(OH)3 2 times a day for 7 days. The animal was then forced to inhale the pollens for challenge, which was restrictively trapped in the upper airways, once a week. Change of specific airway resistance (sRaw), sneezing frequency, and titers of anaphylactic antibodies in the serum were measured after each of the 30 challenges. At the first challenge, no obvious increase in sRaw was observed. However, the second and third challenges to the animals caused modest biphasic elevations of sRaw, with peaks at the first and the fourth to sixth hour. At the fourth to tenth challenges, marked elevations of sRaw were observed. However, with repetition of the inhalation challenge, the early and the late responses became almost indistinguishable because of partial overlapping as the responses expanded. All guinea pigs sneezed immediately after each pollen inhalation challenge. Apparent increases of both circulating gamma1 and IgE antibodies were seen after the seventh challenge. These results indicate that the experimental allergic rhinitis established in the present study can be a valuable model for analyzing the pathogenesis of the disease and developing new therapeutic drugs.

A New Model of Experimental Allergic Rhinitis Using Japanese Cedar Pollen in Guinea Pigs

Ini the majority of the models of experimental allergic rhinitis, antigen challenge has been performed by single topical instillation or perfusion with the solution. The present study was performed to establish a good model using Japanese cedar pollen, which is able to repeatedly induce allergy restricted to the upper airway. Guinea pigs sensitized with the pollen extracts were subjected to quantitative and repeated inhaling of the pollen with a devised apparatus. Following the respective challenges, the nasal cavity was washed with a new technique: Washing with physiologic saline was performed from one nostril to the other one, the latter of which was kept under slightly reduced pressure. When the animal was subjected to cedar pollen inhalation, almost all the pollens inhaled were located in the upper airway. At the 5th inhalation, nasal cavity lavage revealed that both albumin leakage and histamine release into the nasal cavity were increased at maximum levels in 1 hr (respectively 2 mg and 3 ng/animal); and at the same time, a considerable number of leukocytes, especially eosinophils, were found migrating into the nasal cavity for at least 10 hr. The present methods can permit various analyses of allergic rhinitis and the assessment of drugs without sacrificing the animal over the long term.

Molecular characterization of Api g 1, the major allergen of celery (Apium graveolens), and its immunological and structural relationships to a group of 17-kDa tree pollen allergens.

Individuals suffering from immediate hypersensitivity (type-I allergy) to a particular pollen frequently display intolerance to several foods of plant origin. In this respect, individuals sensitized to birch pollen and/or mugwort pollen frequently display type-I allergic symptoms after ingestion of celery. In this study, we expressed the major allergenic protein of celery, Api g 1, which is responsible for the birch-celery syndrome, in the form of a non-fusion protein. The open reading frame of the cDNA of Api g 1 codes for a protein of 153 amino acids with a molecular mass of 16.2 kDa and 40% identity (60% similarity) to the major allergen of birch pollen, Bet v 1. Furthermore, Api g 1 exhibited similar characteristics to (a) two proteins in parsley induced by fungal infection, (b) the major tree pollen allergens and (c) pathogenesis-related and stress-induced proteins in other plant species. The reactivity of recombinant Api g 1 with IgE antibodies present in sera from celery intolerant patients was comparable to that of the natural celery allergen. Cross-reactivity with Bet v 1 was proven by cross-inhibition experiments, which provides further support for the existence of the birch-celery syndrome and for the suggestion that allergies to some vegetable foods are epiphenomena to allergies caused by inhalation of tree pollen.

A Comparison of Acti*Tip™ Allerg*E™ and Allerg*ENS™ System to Phadebas RAST® and Phadebas IgE PRIST® in Assaying Total IgE and Specific IgE in Human Serum

Two in vitro systems of measuring total IgE and specific IgE antibodies were compared using serum of patients suspected of having allergic rhinitis due to inhalation of grass pollen. One in vitro system was the Phadebas PRIST and RAST. The accuracy of these tests has been well defined and they were used as the standard. The Acti*Tip Allerg*E and Allerg*ENS system is a new technique utilizing a similar solid-phase immunologic methodology with an enzyme-based detection system. It has some advantages primarily related to the mechanics of performing the test and marked reduction in time for obtaining results. The correlation between the Phadebas and Acti*Tip systems was highly significant for measuring total IgE and specific IgE antibodies for grasses in serum.

Insoluble and soluble allergens from wheat grain and wheat dust: detection of IgE binding in inhalant and ingestion allergy.

The need for better in vitro testing for wheat allergy particularly involved correlating clinical evidence of Type I hypersensitivity with laboratory detection of specific IgE antibodies in serum. We report here an improvement in this relationship by the use of a modified method for RAST (Radioallergosorbent test), involving nitrocellulose as the solid phase and alkali (or ethanol) for extraction of allergens and treatment of discs. Serum IgE reactions with the full range of wheat grain and dust proteins were studied using this method and the results were related to wheat allergies due to flour ingestion and the inhalation of flour, pollen or grain dust.

IgE antibody responses against Japanese cedar pollen in the mouse.

IgE antibody responses against Japanese cedar pollen in the mouse were investigated to develop a mouse model of human allergy for combinations of factors including pollen administration routes, elicitation antigens and inbred mouse strains. Daily short term inhalation of native pollen or intratracheal administration of pollen suspended in saline induced IgE antibody responses in DBA/2, BDF1 and Balb/c mice, but failed to induce any detectable responses in C57BL/6 and C57BL/10 mice. Intraperitoneal injection of pollen suspension also induced IgE antibody responses in DBA/2, BDF1 and Balb/c mice but not in C57BL/6 mice. IgE antibody responses against pollen described above were detected by passive cutaneous anaphylaxis (PCA) reactions using crude extract of pollen as an elicitation antigen. On the other hand, IgE antibodies specific for antigen Sugi basic protein (AgSBP), which is a major allergen of pollen in humans (Yasueda, H., Yui, Shimizu, T., and Shida, T., 1983. Isolation and partial characterization of the major allergen from Japanese cedar (Cryptomeria japonica) pollen. J. Allergy Clin. Immunol. 71: 77-86), were also detected by PCA reactions using AgSBP in the sera from mice which received secondary or the tertiary stimulation by pollen. These results suggest that IgE antibody responses against Japanese cedar pollen in the mouse can be induced by airway sensitization and that the responses are genetically controlled by H-2-linked immune response genes. The results also suggest that not only IgE antibody responses specific for components other than AgSBP but also responses specific for AgSBP can be induced in the mouse by repeating appropriate sensitization by pollen.

Relationships between plants relevant to allergy.

This article gives background information on the taxonomic relationships between plants, for clinicians, patients and students of allergy. A list is provided of plants considered potentially allergenic either by inhalation of pollen or by ingestion of grain products. Distributions in Australia of plant species important in assessing pollen-related allergy, and the range of foodstuffs that contain cereal-grain protein, are also indicated. Particular emphasis is placed on the grasses because of their importance as producers of both grain and pollen.

Favism and hemolytic anemia in glucose-6-phosphate dehydrogenase-deficient subjects in North Sardinia.

The present paper reports the incidence from 1965 to 1979 of acute hemolytic anemia for a total of 948 cases in G-6-PD-deficient subjects due to the ingestion of fresh or dried fava beans or certain drugs and to viral infections. The highest percentage of hemolytic crises was due to fresh fava beans (94.4%). No cases of favism were observed in breast-fed babies whose mothers had eaten fava beans or from pollen inhalation. The male sex proved to be the hardest hit. Hemoglobin values were lower than or equal to 7 g/dl in about 75% of males and 50% of females. Total bilirubin values were lower than 103 mumol/l (6 mg/dl) in about 75% of males and 85% of females. Both the hemoglobin and bilirubin values were statistically significant. Mean transaminase values (SGPT) were significantly higher than those of normal controls. No correlation between favism and blood groups was found.