Interactive effects of a cysteinyl leukotriene receptor (CysLT1R) antagonist, montelukast (ML), and IL-5 deficiency in murine experimental allergic rhinitis

Morikawa, H., Howie, K., Crawford, L., Cyr, M.M. and Denburg, J.A. (2005) Interactive effects of a cysteinyl leukotriene receptor (CysLT1R) antagonist, montelukast (ML), and IL-5 deficiency in murine experimental allergic rhinitis. Journal of Allergy and Clinical Immunology, 115(2), S194. (doi: 10.1016/j.jaci.2004.12.786)

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Abstract

RATIONALE: Recent studies in murine allergic rhinitis have demonstrated suppressive effects of either IL-5 deficiency or ML on eosinophil recruitment. Neither IL-5 deficiency nor ML alone, however, was sufficient to fully abrogate inflammation or symptoms, due to basophilia and cytokine redundancy in eliciting marrow responses (Saito et al, JI 2002;168:3017; Immunol 2001;104:226). We therefore investigated the combined effects of ML and IL-5 deficiency on in vivo tissue and marrow responses in this model.<p></p> METHODS: Age-matched (8-12 week old) BALB/C mice without or with IL-5 deficiency were placed into one of three groups: two ML-treated groups, given OVAsensitization, and intranasal challenge with oral ML 2.5mg/kg or 5mg/kg; and controls, given OVAsensitization, and challenge with oral sterile water. Nasal symptoms, marrow and nasal mucosal eosinophils and basophils, and bone marrow eosinophil/basophil differentiation (colony-forming units, Eo/B-CFU), were evaluated.<p></p> RESULTS: In IL-5 replete mice, ML treatment significantly decreased the number of eosinophils in both marrow and nasal tissue, and decreased nasal symptoms in a dose-dependent manner, compared to controls. However, in IL-5 deficient mice, ML treatment also significantly decreased the number of basophils in bone marrow and nasal mucosal tissue, further decreased nasal symptoms, and lowered IL-5 responsive Eo/B-CFU ex vivo, compared to controls.<p></p> CONCLUSIONS: These results indicate that ML combines therapeutically with IL-5 deficiency to abrogate both eosinophilic and basophilic responses in experimental allergic rhinitis, suggesting important interactions between cysLT1R and IL-5-IL-5R in allergic inflammation.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stewart, Ms Lynn
Authors: Morikawa, H., Howie, K., Crawford, L., Cyr, M.M., and Denburg, J.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Allergy and Clinical Immunology
Journal Abbr.:J. Allergy Clin. Immunol.
Publisher:Elsevier
ISSN:0091-6749
ISSN (Online):1097-6825

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