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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.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Takeda K,Shiraishi Y,Matsubara S,Miyahara N,Matsuda H,Okamoto M,Joetham A,Gelfand EW

doi

10.1111/j.1476-5381.2010.00797.x

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

1399-407

issue

eissn

0007-1188

issn

1476-5381

pii

BPH797

journal_volume

160

pub_type

杂志文章

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