QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.074922v1 312/2/432    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murai, A. Articles by Tanaka, K. Search for Related Content PubMed PubMed Citation Articles by Murai, A. Articles by Tanaka, K.

INFLAMMATION AND IMMUNOPHARMACOLOGY

Comparison Study between the Mechanisms of Allergic Asthma Amelioration by a Cysteinyl-Leukotriene Type 1 Receptor Antagonist Montelukast and Methylprednisolone

Departments of Pharmacology (M.A., T.K.), Emergency & Critical Care Medicine (A.M., Y.H., K.T.), and Pathology (N.S.), School of Medicine, Fukuoka University, Fukuoka, Japan

We investigated the effects of cysteinyl-leukotriene (cysLT) 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 3 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 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 coaddition 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, 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 cysLT₁ receptor antagonists and steroids for the treatment of asthma.

Address correspondence to: Dr. Masayoshi Abe, Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan. E-mail address: abemasa{at}fukuoka-u.ac.jp

This article has been cited by other articles:

				S. Ito, K. R. Lutchen, and B. Suki Effects of heterogeneities on the partitioning of airway and tissue properties in normal mice J Appl Physiol, March 1, 2007; 102(3): 859 - 869. [Abstract] [Full Text] [PDF]

				M. Abe, S. Jimi, H. Hama, T. Shiraishi, A. Iwasaki, N. Ono, T. Shirakusa, and T. Katsuragi A novel method for preserving human lungs using a super-cooling system. Ann. Thorac. Surg., September 1, 2006; 82(3): 1085 - 1088. [Abstract] [Full Text] [PDF]