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

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-α 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.

• Authors: Yanira Riffo-Vasquez, Francis Man, Clive P Page
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 27 Issue 2 Pg. 170-8 (Apr 2014) ISSN: 1522-9629 [Electronic] England
• PMID: 24456641 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Bronchodilator Agents
• Lipopolysaccharides
• Theophylline
• doxofylline

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Bronchodilator Agents (administration & dosage, pharmacology)
• Cell Movement (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Escherichia coli
• Leukocytes (metabolism)
• Lipopolysaccharides (toxicity)
• Male
• Mice
• Mice, Inbred BALB C
• Pneumonia (drug therapy, physiopathology)
• Theophylline (administration & dosage, analogs & derivatives, pharmacology)