Peters-Golden Marc, Henderson William R
Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan 48109-0642, USA.
Ann Allergy Asthma Immunol. 2005 Jun;94(6):609-18; quiz 618-20, 669. doi: 10.1016/S1081-1206(10)61317-8.
To review the role of cysteinyl leukotrienes (cysLTs) in allergic rhinitis and the scientific rationale for therapy with leukotriene receptor antagonists (LTRAs).
Relevant basic science and clinical articles were identified by a search of the PubMed database for articles published from 1984 to 2004 using the following keywords: allergic rhinitis; nose; immune response; allergen challenge; leukotrienes C, D, and E; cysteinyl leukotriene; cysteinyl leukotriene receptor; cytokine; leukocyte; montelukast; zafirlukast; and pranlukast.
The authors' expert opinion was used to select studies for inclusion in this review.
CysLTs are synthesized via 5-lipoxygenase metabolism of arachidonic acid by mast cells and basophils during the early-phase response to antigen and by eosinophils and macrophages during the late phase. The cysLT levels in nasal secretions are elevated after short-term allergen instillation and in allergy season in patients with allergic rhinitis. These lipid mediators act locally and systemically by interacting with receptors, particularly the cysLT1 receptor, on target cells. Evidence derived from topical application of cysLTs in the nose and from the effects of LTRAs indicates that cysLTs contribute to nasal mucous secretion, congestion, and inflammation. CysLTs promote allergic inflammation by enhancing immune responses and the production, adhesion, migration, and survival of inflammatory cells such as eosinophils. They also increase the generation of an array of other proinflammatory mediators, such as cytokines, which in turn increase the production of and receptors for cysLTs. Clinical trials have demonstrated that LTRAs have significant but modest efficacy as single agents but additive efficacy when used with other classes of agents.
CysLTs fulfill the criteria for relevant mediators of allergic rhinitis via their diverse effects on immune, inflammatory, and local structural components of disease. By blocking the cysLT1 receptor responsible for most of these effects, LTRAs represent a useful approach to treatment of this important and prevalent disorder.
综述半胱氨酰白三烯（cysLTs）在变应性鼻炎中的作用以及白三烯受体拮抗剂（LTRAs）治疗的科学依据。
通过检索PubMed数据库，使用以下关键词查找1984年至2004年发表的相关基础科学和临床文章：变应性鼻炎；鼻；免疫反应；变应原激发；白三烯C、D和E；半胱氨酰白三烯；半胱氨酰白三烯受体；细胞因子；白细胞；孟鲁司特；扎鲁司特；和普仑司特。
作者的专家意见用于选择纳入本综述的研究。
在抗原早期反应期间，肥大细胞和嗜碱性粒细胞通过花生四烯酸的5-脂氧合酶代谢合成cysLTs，在晚期则由嗜酸性粒细胞和巨噬细胞合成。变应性鼻炎患者短期变应原滴注后以及在过敏季节，鼻分泌物中的cysLT水平升高。这些脂质介质通过与靶细胞上特定受体（尤其是cysLT1受体）相互作用，在局部和全身发挥作用。鼻腔局部应用cysLTs以及LTRAs的作用所获得的证据表明，cysLTs会导致鼻黏液分泌、充血和炎症。CysLTs通过增强免疫反应以及嗜酸性粒细胞等炎症细胞的产生、黏附、迁移和存活来促进变应性炎症。它们还会增加一系列其他促炎介质（如细胞因子）的生成，而这些细胞因子反过来又会增加cysLTs的产生和受体。临床试验表明，LTRAs作为单一药物具有显著但适度的疗效，与其他类药物联合使用时具有相加疗效。
CysLTs通过对疾病的免疫、炎症和局部结构成分产生多种影响，符合变应性鼻炎相关介质的标准。通过阻断负责这些大多数作用的cysLT1受体，LTRAs是治疗这一重要且常见疾病的一种有效方法。
