Astım ve lökotrienler

Amaç: Geçtiğimiz on yılda, astım patogenezi hakkındaki temel kavramlar özellikle hastalığın karakteristik bir özelliği olan remodelling ve havayolu inflamasyonu konularında önemli bir şekilde değişmiştir. Bu yazı, astım patogenezinde lökotrienler üzerine yoğunlaşan bir derlemedir. Ana bulgular: Astımlılarda hava yolu anormalliklerinin gelişiminde hücresel mediatörlerin oluşumu ve salınımı bildirilmiş ve gösterilmiştir. Lipit mediatörler, lökotrienler, allerjenle karşılaştıktan dakikalar sonra üretilir. Araşidonik asit metabolizmasında sikloksijenaz yolu ile PGD2, PGF2a ve tromboksan içeren prostaglandinler oluşur, bunların tümü bronkokonstriksiyon ile ilişkilidir. Lipooksijenaz enzim yolu sistenil lökotrienlerin (LTC4, LTD4 ve LTE4) ve LTB4’ün üretimini sağlar. LTB4, alveoler makrofajlar ve nötrofillerde üretilen majör lipooksijenaz ürünüdür. Sistenil lökotrienler, bronş düz kasında kasılmaya sekresyonlarda artışa ve mikrovasküler dolaşımda dışarı plazma sızmasına neden olur. In vivo bu durum hava yolu mukus sekresyonunda artışa ve bronş aşırı duyarlılığına sebep olur. Son olarak çalışmalar, LTE4 inhalasyonunun hava yoluna, eozinofil toplanmasına, dolayısıyla eozinofilik enflamasyona katkısı olduğunu düşündürmektedir. Sonuç: Astımın değişik varyasyonları ve kronik persistan astımda lökotrienlerin katkısı hakkındaki klinik kanıtlar 5-lipoxygenase inhibitörleri ve LTD4 reseptör antagonistleri ile çalışmalardan elde edilen sonuçlardır ve astım oluşumu üzerinde etkinlikleri gösterilmiştir.

Anahtar Kelimeler:

Lökotrienler, Astım, Enflamasyon

The leukotrienes and asthma

Objective: Concepts about asthma pathogenesis have changed dramatically in the past decade with a new focus on airway inflammation and remodeling as characteristic features of the disease and fundamental links to its pathogenesis. These review focuses on the leukotrienes in asthma pathogenesis. Main findings: The development of airway abnormalities in asthma is dictated and directed by the release and generation of cell- derived mediators. The lipid mediators, leukotriens, are produced within minutes of an allergen challenge. Arachidonic acid metabolism via the cyclooxygenase pathway produces prostaglandins, including PGD2, PGF2a and tromboxane, all of which have bronchoconstrictor activity. Lipoxygenase enzyme pathway products include the leukotrienes, including LTB4, as well as cystenil leukotrienes, LTC4, LTD4 and LTE4. LTB4 is a major lipooxygenase product of the alveolar macrophages and neutrophils. The cysteinyl leukotrienes, all contract airway smooth muscle and increase glandular secretion and initiate microvascular plasma leak. In vivo, these compounds increase airway mucus production and cause increased airway hyperresponsiveness in asthmatic subjects compared with normal controls. Finally, preliminary data suggest that inhaled LTE4 can attract eosinophils to the airway, thus perpetuating the development of eosinophilic inflammation. Conclusion: Clinical evidence for the contribution of leukotrienes to asthma is further derived from studies with 5-lipoxygenase inhibitors and LTD4 receptor antagonists, which show effectiveness in various models of asthma and chronic persistent disease.

Keywords:

Leukotrienes, Asthma, Inflammation,

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