Received for publication July 26, 2004.
Revised September 27, 2004.
Accepted for publication September 28, 2004.

Comparison study between the mechanisms of allergic asthma amelioration by a cysteinyl-leukotriene type 1 receptor antagonist, montelukast, and methylprednisolone

Abstract

We investigated the effects of cysteinyl-leukotriene type 1 receptor antagonist, montelukast (MK), and compared them with those of methylprednisolone (MP) in an allergic asthma model. Rats sensitized to ovalbumin (OVA) received repeated intratracheal exposure to OVA for up to three consecutive days. Pretreatment with MK or MP before OVA exposure inhibited late airway response (LAR) and reduced cellular infiltration into the bronchial submucosa after the triple OVA. The amount of N-acetyl-leukotriene E₄ in the bile was significantly reduced by pretreatment with MK or MP, suggesting that both drugs reduced the production of cysteinyl-leukotrienes (cysLTs) in the lungs. In the in vitro study, when the fragments of lungs that had been repeatedly pretreated with MK or MP and exposed to OVA were removed and incubated with OVA, the co-addition of either drug significantly reduced cysLT production. In contrast, the cysLT production following the addition of OVA to the lung fragments that had not received in vivo pretreatment with either drug was inhibited by MK, but not by MP. These results indicate that MK and MP inhibit LAR by suppressing the infiltration of inflammatory cells into the bronchial submucosa and thereby inhibiting the production of cysLTs in the lungs, and that MK, but not MP, may inhibit cysLT production directly. The different effects on cysLT production between the two drugs may provide a rationale for the use of combination therapy with cysLT₁RAs and steroids for treatment of asthma.

Key words: N-acetyl-LTE4, airway inflammation, asthma, cysteinyl-leukotriene type 1 receptor antagonist, late airway response, steroid

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