Effect of montelukast on basophil releasability in patients with asthma.

BACKGROUND The anti-inflammatory effect of montelukast, a leukotriene receptor antagonist, in patients with bronchial asthma is not entirely clear. Basophils can release a variety of mediators, including histamine and leukotriens, which most likely play an active role in the late allergic response. OBJECTIVES To study the effect of montelukast (10 mg/day) on histamine and cysteinyl leukotriene release from basophils taken from 12 mild atopic asthmatic patients who took the drug for 4 weeks. METHODS Basophils were withdrawn at baseline, and after 48 hours, 1 week, and 4 weeks of therapy. Histamine was measured by a radioenzymatic method and leukotrienes by immunologic assay. Histamine and cysLT release was measured spontaneously and following stimulation with interleukin-3 and anti-immunoglobulin E. Spirometry and symptom score were measured before and during treatment. RESULTS During the treatment with montelukast there were no significant changes in spontaneous, IL-3 and anti-IgE-induced histamine release. cysLT release decreased significantly only after 4 weeks of treatment (from 2899 +/- 550 pg/ml at baseline to 2225 +/- 430 pg/ml at 4 weeks, P= 0.02). CONCLUSIONS Montelukast does not seem to affect the release of histamine from basophils but mildly inhibits the cysLT release seen after 4 weeks of treatment.

[1]  A. Baatjes,et al.  Expression of functional cysteinyl leukotriene receptors by human basophils. , 2005, The Journal of allergy and clinical immunology.

[2]  M. Triggiani,et al.  Pharmacological modulation of human mast cells and basophils , 2002, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[3]  L. J. Woods,et al.  Intracrine Cysteinyl Leukotriene Receptor–mediated Signaling of Eosinophil Vesicular Transport–mediated Interleukin-4 Secretion , 2002, The Journal of experimental medicine.

[4]  K. Austen,et al.  Cysteinyl Leukotrienes and Uridine Diphosphate Induce Cytokine Generation by Human Mast Cells Through an Interleukin 4–regulated Pathway that Is Inhibited by Leukotriene Receptor Antagonists , 2002, The Journal of experimental medicine.

[5]  P. Kuna,et al.  A randomized, double-blind trial of the effect of treatment with montelukast on bronchial hyperresponsiveness and serum eosinophilic cationic protein (ECP), soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion molecule 1 (sICAM-1) in children with asthma. , 2002, The Journal of allergy and clinical immunology.

[6]  J. Schroeder,et al.  Inhibition of cytokine generation and mediator release by human basophils treated with desloratadine , 2001, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[7]  M. Ennis,et al.  Laboratory‐based allergy diagnosis: should we go with the flow? , 2001, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[8]  Franco H Falcone,et al.  The human basophil: a new appreciation of its role in immune responses. , 2000, Blood.

[9]  M. Church,et al.  Non‐H1‐receptor effects of antihistamines , 1999, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[10]  L. Larsson,et al.  Selective effects of antileukotrienes on leukotriene and histamine release in human dispersed lung cells , 1999, Inflammation Research.

[11]  E. Israel,et al.  Correction: Treatment of Asthma with Drugs Modifying the Leukotriene Pathway. , 1999, The New England journal of medicine.

[12]  A. Onn,et al.  The in vitro and in vivo effect of corticosteroides on basophi releasabihty in patients with mild and severe bronchial asthma , 1997, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[13]  Y. Levo,et al.  A comparison of the inhibitory effect of cromoline and nedocromil Na on histamine release from airway metachromatic cells and from peripheral basophils. , 1996, Immunology letters.

[14]  E. Israel,et al.  Diurnal variation of urinary leukotriene E4 and histamine excretion rates in normal subjects and patients with mild-to-moderate asthma. , 1995, The Journal of allergy and clinical immunology.

[15]  E. Fireman,et al.  The effect of exercise on basophil histamine release in patients with bronchial asthma. , 1994, Immunology letters.

[16]  C. Dahinden,et al.  The degradation product of the C5a anaphylatoxin C5adesarg retains basophil‐activating properties , 1994, European journal of immunology.

[17]  S. Galli,et al.  Identification of IgE-bearing cells in the late-phase response to antigen in the lung as basophils. , 1994, American journal of respiratory cell and molecular biology.

[18]  T. Haahtela,et al.  Leukotriene E4 and granulocytic infiltration into asthmatic airways , 1993, The Lancet.

[19]  Robert A. Lewis,et al.  Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. , 1990, The New England journal of medicine.

[20]  S. Peters,et al.  Differential Release of Mediators From Human Basophils: Differences in Arachidonic Acid Metabolism Following Activation by Unrelated Stimuli , 1989, Journal of leukocyte biology.

[21]  A. Kreft,et al.  Inhibition of platelet and neutrophil phospholipase A2 by hydroxyeicosatetraenoic acids (HETES). A novel pharmacological mechanism for regulating free fatty acid release. , 1985, Biochemical pharmacology.

[22]  M. Church,et al.  INHIBITION OF HISTAMINE RELEASE FROM HUMAN LUNG in vitro BY ANTIHISTAMINES AND RELATED DRUGS , 1980, British journal of pharmacology.

[23]  A. D. de Weck,et al.  Cellular allergen stimulation test (CAST) 2003, a review. , 2004, Journal of investigational allergology & clinical immunology.

[24]  E. Fireman,et al.  Effect of nedocromil sodium and cromoline sodium on atopic basophil function. , 1996, International journal of immunopharmacology.

[25]  L. Lichtenstein,et al.  Immunological aspects of allergic asthma. , 1994, Annual review of immunology.