Effects of combination therapy with montelukast and carbocysteine in allergen-induced airway hyperresponsiveness and airway inflammation.

Abstract

BACKGROUND AND PURPOSE:

Montelukast and S-carbocysteine have been used in asthmatic patients as an anti-inflammatory or mucolytic agent respectively. S-carbocysteine also exhibits anti-inflammatory properties.

EXPERIMENTAL APPROACH:

Ovalbumin (OVA) sensitized BALB/c mice were challenged with OVA for 3 days followed by single OVA re-challenge (secondary challenge) 2 weeks later. Forty-eight hours after secondary challenge, mice were assessed for airway hyperresponsiveness (AHR) and cell composition in bronchoalveolar lavage (BAL) fluid. Suboptimal doses of 10 mg.kg(-1) of S-carbocysteine by intraperitoneal injection (ip), 20 mg.kg(-1) of montelukast by gavage, the combination of S-carbocysteine and montelukast or 3 mg.kg(-1) of dexamethasone as a control were administered from 1 day before the secondary challenge to the last experimental day. Isolated lung cells were cultured with OVA and montelukast to determine the effects on cytokine production.

KEY RESULTS:

Treatment with S-carbocysteine or montelukast reduced both AHR and the numbers of eosinophils in BAL fluid. Neutralizing IFN-gamma abolished the effects of S-carbocysteine on these airway responses. Combination of the two drugs showed further decreases in both AHR and eosinophils in the BAL fluid. Goblet cell metaplasia and Th2-type cytokines, interleukin (IL)-4, IL-5 and IL-13, in BAL fluid were decreased with montelukast treatment. Conversely, S-carbocysteine increased Th1-type cytokines, IFN-gamma and IL-12 in BAL fluid.

CONCLUSIONS AND IMPLICATIONS:

The combination of two agents, montelukast and S-carbocysteine, demonstrated additive effects on AHR and airway inflammation in a secondary allergen model most likely through independent mechanisms of action.

• Authors: K Takeda, Y Shiraishi, S Matsubara, N Miyahara, H Matsuda, M Okamoto, A Joetham, E W Gelfand
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 160 Issue 6 Pg. 1399-407 (Jul 2010) ISSN: 1476-5381 [Electronic] England
• PMID: 20590630 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Acetates
• Anti-Asthmatic Agents
• Anti-Inflammatory Agents
• Cyclopropanes
• Quinolines
• Sulfides
• Carbocysteine
• Dexamethasone
• Ovalbumin
• montelukast

Topics

• Acetates (administration & dosage, pharmacology)
• Animals
• Anti-Asthmatic Agents (administration & dosage, pharmacology)
• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Bronchial Hyperreactivity (drug therapy, immunology)
• Bronchoalveolar Lavage Fluid
• Carbocysteine (administration & dosage, pharmacology)
• Cyclopropanes
• Dexamethasone (pharmacology)
• Drug Synergism
• Drug Therapy, Combination
• Eosinophils (metabolism)
• Female
• Inflammation (drug therapy, immunology)
• Injections, Intraperitoneal
• Mice
• Mice, Inbred BALB C
• Ovalbumin (immunology)
• Quinolines (administration & dosage, pharmacology)
• Sulfides