Montelukast prevents the decrease of interleukin-10 and inhibits NF-kappaB activation in inflammatory airway of asthmatic guinea pigs.

Abstract

Interleukin (IL)-10 is an important immunoregulatory and anti-inflammatory cytokine, whereas nuclear factor-kappaB (NF-kappaB) plays an important role in the pathogenesis of asthma. In the present study, the effects of montelukast on the level of IL-10 and on the activation of NF-kappaB in the inflammatory airway of asthmatic guinea pigs were investigated. Guinea pigs were sensitized by ovalbumin. Pulmonary inflammation was observed by hematoxylin and eosin staining. The eosinophils in broncho-alveolar lavage fluid and blood were separated by density gradient centrifugation and counted under microscope. The level of IL-10 in broncho-alveolar lavage fluid was measured by enzyme-linked immunoadsorbent assay. Activation of NF-kappaB in lung tissues was inspected by immunohistochemistry. Montelukast at medium and high doses prevented the decrease of IL-10 in broncho-alveolar lavage fluid (n = 8, p < 0.01 vs. asthma model group), inhibited the activation of NF-kappaB in lung tissues (n = 8; medium dose, p < 0.05; high dose, p < 0.01; vs. asthma model group). There was a significantly negative correlation between the level of IL-10 and the activation of NF-kappaB in lung tissues (r = -0.488, p < 0.01). Montelukast reduced the severity of airway inflammation and the number of eosinophils in asthmatic guinea pigs. From all these findings we conclude that montelukast can prevent the decrease of IL-10 and inhibit the activation of NF-kappaB in inflammatory airway of asthmatic guinea pigs, which may be the new important mechanisms of montelukast's anti-airway-inflammation effects in asthmatic guinea pigs.

• Authors: Yuqing Wu, Chenghua Zhou, Jin Tao, Shengnan Li
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 84 Issue 5 Pg. 531-7 (May 2006) ISSN: 0008-4212 [Print] Canada
• PMID: 16902598 (Publication Type: Journal Article)

Chemical References

• Acetates
• Anti-Asthmatic Agents
• Cyclopropanes
• Leukotriene Antagonists
• NF-kappa B
• Quinolines
• Sulfides
• Interleukin-10
• montelukast

Topics

• Acetates (pharmacology)
• Animals
• Anti-Asthmatic Agents (pharmacology)
• Asthma (drug therapy, immunology)
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Cyclopropanes
• Eosinophils (drug effects, immunology)
• Guinea Pigs
• Interleukin-10 (immunology)
• Leukocyte Count
• Leukotriene Antagonists (pharmacology)
• Lung (drug effects, pathology)
• Male
• NF-kappa B (immunology)
• Quinolines (pharmacology)
• Sulfides