An experimental allergic conjunctivitis induced by topical and repetitive applications of Japanese cedar pollens in guinea pigs

Yasuda, Manabu; Kato, Masatomo; Nabe, Takeshi; Nakata, Katsuhiko; Kohno, Shigekatsu

doi:10.1007/s000110050468

Cited by 14 publications

(23 citation statements)

References 26 publications

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“…In the present study, we evaluated whether the histamine involvement in the causation of symptoms is altered during multiple pollen challenges in our recently developed guinea pig model for Japanese cedar pollen-induced allergic conjunctivitis. 10) In most clinical and experimental settings of ocular allergy, pharmacologically active compounds are usually applied as eye drops in order to localize them at a high concentration. 4,5,19,20) However, it is well known that topically applied drugs are rapidly drained into the nasopharyngeal cavity through the nasopharyngeal duct.…”

Section: Discussionmentioning

confidence: 99%

“…Sensitization, Challenge, and Treatment with Drugs As previously described, 10) guinea pigs were sensitized systemically by intraperitoneal injections with the extractsϩ Al(OH) 3 twice within a week at a dose of 10 mg pollen protein/20 mg Al(OH) 3 /ml/animal/time. On the 21st day after the first sensitization, the sensitized animals were challenged by the dropping of a pollen suspension without Al(OH) 3 in each of their eyes at a dose of 2 mg pollens/10 ml/eye.…”

Section: Methodsmentioning

confidence: 99%

“…To address this situation, we have developed a guinea pig model of allergic conjunctivitis in which sensitized animals are repeatedly challenged by the dropping of a Japanese cedar pollen suspension in the eye. 10) We previously reported that the multiple challenge approach aggravates the disease in proportion to the number of challenges. 10) In the present study, we evaluated whether involvement of histamine in the induction of symptoms of allergic conjunctivitis is altered by the multiple pollen challenges in the model.…”

mentioning

confidence: 99%

“…10) We previously reported that the multiple challenge approach aggravates the disease in proportion to the number of challenges. 10) In the present study, we evaluated whether involvement of histamine in the induction of symptoms of allergic conjunctivitis is altered by the multiple pollen challenges in the model. In addition, in order to know a part of mechanisms underlying the histamine-independent allergic conjunctivitis, we determined whether the symptoms mediated by nitric oxide (NO) synthesis.…”

mentioning

confidence: 99%

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Multiple Cedar Pollen Challenge Diminishes Involvement of Histamine in Allergic Conjunctivitis of Guinea Pigs

Fukushima

Nabe

Mizutani

et al. 2003

Biological & Pharmaceutical Bulletin

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Allergic conjunctivitis is one of the typical atopic diseases. Recently, a number of patients in Japan have been suffering from Japanese cedar pollinosis with symptoms that include allergic rhinitis and conjunctivitis. The prevalence of allergic conjunctivitis is estimated to occur in approximately 20% of the general Japanese population. The ocular allergy is characterized by severe itching, hyperemia and edema. Medical therapy consists of topical applications of antihistamines with or without vasoconstrictors, mast cell stabilizers, nonsteroidal anti-inflammatory drugs and glucocorticoids. 1)Among these treatments, antihistamine is one of the most common medications for allergic conjunctivitis. 1) However, Howarth 2) has suggested that antihistamines do not fully modify the disease since histamine is not the only contributor to symptom generation in allergic conjunctivitis. Despite the existence of a histamine-independent mechanism, in the majority of experimental allergic conjunctivitis models, antihistamines are significantly effective in the reduction of symptoms. [3][4][5] Most experimental ocular allergy animal models have been developed by actively sensitizing guinea pigs with an intraperitoneal injection of a non-airborne antigen such as ovalbumin 6) and dinitrophenylated lysine 7) mixed with an adjuvant or by passively sensitizing animals with antisera, 8,9) which is followed by the subsequent single conjunctival challenge with a solution of the specific antigen. These models are considerably different from the clinical situation because the antigen challenges are not performed chronically. To address this situation, we have developed a guinea pig model of allergic conjunctivitis in which sensitized animals are repeatedly challenged by the dropping of a Japanese cedar pollen suspension in the eye.10) We previously reported that the multiple challenge approach aggravates the disease in proportion to the number of challenges.10) In the present study, we evaluated whether involvement of histamine in the induction of symptoms of allergic conjunctivitis is altered by the multiple pollen challenges in the model. In addition, in order to know a part of mechanisms underlying the histamine-independent allergic conjunctivitis, we determined whether the symptoms mediated by nitric oxide (NO) synthesis. MATERIALS AND METHODSAnimals Male, 3-week-old, Hartley guinea pigs weighing 250-300 g were purchased from Japan SLC, Hamamatsu, Japan. The animals were housed in an air-conditioned room at a temperature of 23Ϯ1°C and 60Ϯ10% humidity with a controlled 12 h light/dark cycle, and fed a standard laboratory diet with water given ad libitum. The first sensitization was started 1-2 weeks after the purchase. The Experimental Animal Research Committee at Kyoto Pharmaceutical University approved this animal study.Materials The following reagents were obtained from the indicated commercial sources: mepyramine maleate and L-arginine hydrochloride (Sigma Chem., St. Louis, MO, U.S.A.); N w -nitro-L-arginine methyl ester (L-NAME) ...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Multiple Cedar Pollen Challenge Diminishes Involvement of Histamine in Allergic Conjunctivitis of Guinea Pigs

Fukushima

Nabe

Mizutani

et al. 2003

Biological & Pharmaceutical Bulletin

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“…Secondly, eosinophils as well as mast cells play roles in the symptoms caused by the repetitive antigen challenge, and eosinophil granule proteins such as EPO were detected in the tear fluid, indicating that the model is well correlated with the pathophysiology of patients with allergic conjunctivitis. Yasuda et al have previously reported the benefits of repetitive antigen challenge models of allergic conjunctivitis in guinea pigs (25).…”

Section: Discussionmentioning

confidence: 99%

Apafant, a Potent Platelet-Activating Factor Antagonist, Blocks Eosinophil Activation and Is Effective in the Chronic Phase of Experimental Allergic Conjunctivitis in Guinea Pigs

et al. 2004

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Abstract. Platelet-activating factor (PAF) plays important roles in allergic reactions. In particular, there are many concerns about PAF, eosinophils, and the chronicity of allergic diseases. The purpose of the present studies is to elucidate the role of PAF in eosinophil activation at conjunctiva and to confirm the efficacy of Apafant (a potent PAF antagonist) ophthalmic solution in chronic experimental allergic conjunctivitis. Guinea pigs were actively immunized and allergic conjunctivitis was induced by repetitive instillation of 2.5% ovalbumin. PAF solution was topically applied and eosinophil activation was assessed by measuring the eosinophil peroxidase (EPO) activity in the tear fluid. Itch-scratching episodes and clinical symptoms scores were evaluated in the repetitive challenge conjunctivitis. From the instillation of PAF solution into guinea pig eyes, which were in a state of chronic allergic conjunctivitis, a significant increase in EPO activity was observed, and this increase was inhibited by pretreatment with Apafant. In the repetitive challenge model, the animals treated with Apafant ophthalmic solution showed a significant reduction of clinical symptoms and the itch-scratch response in both the first and the second challenges. PAF has an activity, that induces mediator release from eosinophils in the conjunctival tissues and may be involved in the chronic phase of allergic conjunctivitis.

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Induction of oral tolerance to Japanese cedar pollen

et al. 2001

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Oral tolerance is thought to play a role in preventing allergic responses and immune-mediated diseases. An improved mouse model of the oral tolerance to Japanese cedar pollen (JCP) as antigen was developed in order to detect induction of the tolerance, and the immunological characteristics of this model were also elucidated. Oral tolerance was induced by C3H/ HeN mice given an oral administration of 10 mg JCP 7 days before immunization with an i.p. injection of 0.1 mg JCP in complete Freunds adjuvant (CFA). The effects of oral JCP on systemic immunity were assessed by enzyme-linked immunosorbent assay (ELISA) of immunoglobulin (Ig) levels in serum collected on day 7 or 14 after immunization. Oral tolerance to JCP was adequately induced on day 7 after immunization and was more effective in C3H/HeN mice than in BALB/c mice. The tolerance was primarily concerned with the decreased serum levels of antigen-specific IgG. In these mice, oral administration of JCP also suppressed various immune responses to the antigen including delayed-type hypersensitivity (DTH), total IgE level and anti-JCP IgG1 level. The suppression of these immune responses by the oral antigen was associated with a significant reduction in interleukin-4 (IL-4) production. These findings therefore indicate that this C3H/HeN mice model has potential use in detecting the induction of oral tolerance by JCP, and suggest that this tolerance model may be effective in the treatment and prevention of allergic responses caused by the antigen.

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An experimental allergic conjunctivitis induced by topical and repetitive applications of Japanese cedar pollens in guinea pigs

Cited by 14 publications

References 26 publications

Multiple Cedar Pollen Challenge Diminishes Involvement of Histamine in Allergic Conjunctivitis of Guinea Pigs

Multiple Cedar Pollen Challenge Diminishes Involvement of Histamine in Allergic Conjunctivitis of Guinea Pigs

Apafant, a Potent Platelet-Activating Factor Antagonist, Blocks Eosinophil Activation and Is Effective in the Chronic Phase of Experimental Allergic Conjunctivitis in Guinea Pigs

Induction of oral tolerance to Japanese cedar pollen

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