スギ花粉を用いた実験的アレルギー性鼻炎に関する研究 : アレルギー性鼻炎症状におけるCysteinyl Leukotrienesの役割について

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Cysteinyl leukotrienes (CysLTs: LTC_4, LTD_4, and LTE_4) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of allergic rhinitis. Because treatment with a CysLT_1 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 LTD_4 induced by repetitive inhalation challenge with Japanese cedar pollen. In this model, the CysLT_1 receptor antagonist pranlukast suppressed the late-phase nasal blockage but not early blockage and sneezing. Nasal hyperresponsiveness (nasal blockage) to LTD_4 was largely blocked by pranlukast, naphazoline, and N^ω-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 CysLT_1 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.
公益社団法人日本薬学会の論文
2003-01-01

スギ花粉を用いた実験的アレルギー性鼻炎に関する研究 : アレルギー性鼻炎症状におけるCysteinyl Leukotrienesの役割について

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