Role of Leukotriene B4 Receptor Antagonist in Pulmonary Fibrosis

Review article


Takehiro Izumo, Mitsuko Kondo, Naoki Arai and Atsushi Nagai

Affiliation: First Department of Medicine, Tokyo Women’s Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan


ABSTRACT

Leukotrienes (LTs) are important chemoattractants for leukocytes and play a pivotal role in the pathogenesis of inflammatory and immune disease, and recent evidence suggests that LTs also play an important role in pulmonary fibrosis. The synthesis of leukotriene B4 (LTB4) and cysteinyl leukotriene (cysLT) is catalyzed by 5‐lipoxygenase. Elevated levels of LTB4 in bronchial alveolar lavage fluid have been reported in allergic diseases and pulmonary fibrosis. Recent reports using LTB4 receptor (BLTR) antagonists have revealed that ligation of BLTR by LTB4 is important for the activation and recruitment of inflammatory cells including neutrophils, eosinophils, monocyte/macrophages, and T cells to inflamed tissues in inflammatory diseases. Although it is about 30 years since LTB4 was discovered in 1979, recent research about BLTR antagonists has revealed the important roles of the LTB4/BLTR pathway in the pathophysiology of pulmonary diseases, such as bronchial asthma and pulmonary fibrosis. We reported recently that BLTR antagonists inhibited the development of bleomycin‐induced pulmonary fibrosis in mice by decreasing the inflammation and altering transforming growth factor β, interleukin (IL)‐6, IL‐13, and interferon γ. Current therapy for pulmonary fibrosis is ineffective, and the disease has a poor outcome and is associated with severe morbidity. Corticosteroid therapy for pulmonary fibrosis is not effective and does not prevent progression. Targeting of the LTB4/BLTR pathway may be an important strategy in the treatment of pulmonary fibrosis.

Keywords: pulmonary fibrosis, leukotriene B4, leukotriene B4 receptor (BLTR), leukotriene B4 receptor antagonist, cysteinyl leukotriene
Correspondence: Takehiro Izumo, First Department of Medicine, Tokyo Women’s Medical University, School of Medicine, 8‐1 Kawada‐cho, Shinjuku‐ku, Tokyo, 162‐8666, Japan. Tel: (81)‐3‐3353‐8111; Fax: (81)‐3‐5379‐5457; e‐mail: drtake@s6.dion.ne.jp