Effects of a leukotriene B4 receptor antagonist on bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis. Leukotrienes play an important role in IPF, and leukotriene (LT)B(4) is one of the key eicosanoids in IPF. In this study, we investigated whether ONO-4057, a LTB(4) receptor (BLTR) antagonist is capable of preventing bleomycin-induced pulmonary fibrosis. On day 1, C57BL/6 male mice were given a single intratracheal injection of bleomycin (2.5 mg x kg(-1)), and ONO-4057 (1.0 mg x kg(-1)) or vehicle alone, administered by intraperitoneal injection on days 1-5 each week for 3 weeks after the bleomycin injection. ONO-4057 reduced the total cell count in bronchoalveolar lavage fluid (BALF) on days 7, 14 and 21 and the Ashcroft score and the lung hydroxyproline content on days 14 and 21. The LTB(4), interleukin (IL)-6, IL-13, transforming growth factor (TGF)-beta levels in BALF and the TGF-beta expression in lung tissue, assessed by immunohistochemistry were decreased on day 7, whereas interferon (IFN)-gamma level in BALF was increased on day 14. The results of this study indicated that the BLTR antagonist inhibited the development of bleomycin-induced pulmonary fibrosis in mice by decreasing inflammation and altering TGF-beta, IL-6, IL-13 and IFN-gamma.
AuthorsT Izumo, M Kondo, A Nagai
JournalThe European respiratory journal (Eur Respir J) Vol. 34 Issue 6 Pg. 1444-51 (Dec 2009) ISSN: 1399-3003 [Electronic] Switzerland
PMID19460787 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibiotics, Antineoplastic
  • Immunosuppressive Agents
  • Interleukin-13
  • Interleukin-6
  • Phenylpropionates
  • Receptors, Leukotriene B4
  • Transforming Growth Factor beta
  • Bleomycin
  • ONO-LB 457
  • Interferon-gamma
  • Animals
  • Antibiotics, Antineoplastic (toxicity)
  • Bleomycin (toxicity)
  • Bronchoalveolar Lavage Fluid
  • Immunohistochemistry (methods)
  • Immunosuppressive Agents (pharmacology)
  • Interferon-gamma (metabolism)
  • Interleukin-13 (metabolism)
  • Interleukin-6 (metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phenylpropionates (pharmacology)
  • Prognosis
  • Pulmonary Fibrosis (chemically induced, prevention & control)
  • Receptors, Leukotriene B4 (antagonists & inhibitors)
  • Transforming Growth Factor beta (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: