NDLI: Doxofylline, a novofylline inhibits lung inflammation induced by lipopolysacharide in the mouse.

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Doxofylline, a novofylline inhibits lung inflammation induced by lipopolysacharide in the mouse.

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Doxofylline, a novofylline inhibits lung inflammation induced by lipopolysacharide in the mouse.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Riffo-Vasquez, Yanira Man, Francis Page, Clive P.
Description	Author Affiliation: Riffo-Vasquez Y ( Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, UK. Electronic address: yanira.vasquez@kcl.ac.uk.); Man F ( Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, UK.); Page CP ( Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, UK.)
Abstract	RATIONAL: Doxofylline is a xanthine drug that has been used as a treatment for respiratory diseases for more than 30 years. In addition to doxofylline being a bronchodilator, some studies have indicated that doxofylline also has anti-inflammatory properties, although little is known about the effect of this drug on lung inflammation. OBJECTIVES: We have investigated the actions of doxofylline against the effects of Escherichia coli LPS in the lungs of BALB/c mice. METHODS: Animals have been treated with doxofylline (0.1, 0.3 and 1 mg/kg i.p.) 24, -and 1 h before, and 6 h after intra-nasal instillation of LPS (10 µg/mouse). Readouts were performed 24 h later. RESULTS: Doxofylline at 1 and 0.3, but not at 0.1 mg/kg, significantly inhibit neutrophil recruitment to the lung induced by LPS (LPS: 208.4 ± 14.5 versus doxofylline: 1 mg/kg: 106.2 ± 4.8; 0.3 mg/kg: 105.3 ± 10.7 × 10(4) cells/ml). Doxofylline significantly inhibited IL-6 and TNF- release into BAL fluid in comparison to LPS-treated animals (LPS: 1255.6 ± 143.9 versus doxofylline 1 mg/kg: 527.7 ± 182.9; 0.3 mg/kg: 823.2 ± 102.3 pg/ml). Intra-vital microscopy of the tracheal tissue demonstrated that doxofylline significantly reduced LPS-mediated leukocyte adhesion to the vessel wall (LPS: 5.9 ± 2.4 versus doxofylline 0.3 mg/kg: 1.78 ± 0.87 cells/100 µm/15 s). Similarly, intra-vital microscopy of cremaster muscle demonstrated that doxofylline significantly reduced LPS-mediated leukocyte transmigration across the blood vessel wall (LPS: 9.3 ± 3.5 versus doxofylline0.3 mg/kg: 3.1 ± 1.87 cells/100 µm(2)). Doxofylline (0.1-10 µM) also reduced fMLP-induced leukocyte migration in vitro, achieving a maximum effect at 10 µM (fMLP: 37.8 ± 0.5 versus doxofylline 10 µM: 15.1 ± 1.2 cells × 10(4)/ml). CONCLUSION: Doxofylline inhibits LPS-induced inflammation in the lungs of mice.
File Format	HTM / HTML
ISSN	10945539
Issue Number	2
Volume Number	27
e-ISSN	15229629
Journal	Pulmonary Pharmacology & Therapeutics
Language	English
Publisher	Elsevier
Publisher Date	2014-04-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Discipline Pulmonary Medicine Anti-inflammatory Agents Pharmacology Bronchodilator Agents Pneumonia Drug Therapy Theophylline Analogs & Derivatives Animals Administration & Dosage Cell Movement Drug Effects Disease Models, Animal Dose-response Relationship, Drug Escherichia Coli Leukocytes Metabolism Lipopolysaccharides Toxicity Male Mice Mice, Inbred Balb C Physiopathology Journal Article
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Pulmonary and Respiratory Medicine Pharmacology (medical)

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