Abstract | BACKGROUND: METHODS: RESULTS: Production of IL-4, IL-5, and GM-CSF by mononuclear cells under stimulation with mite antigen was markedly suppressed when they were exposed to ONO-1078 at a concentration of 10 microg/mL. CONCLUSION: The results suggest that ONO-1078 acts directly on peripheral blood mononuclear cells and that blockade of leukotriene receptors on blood mononuclear cells by the cysteinyl-leukotriene receptor antagonist (LTRA) pranlukast (ONO-1078) can dose-dependently inhibit release of immunoreactive TH2-type cytokines (IL-3, IL-4, GM-CSF, and possibly IL-5), but not of the TH1-type cytokine IL-2, when stimulated by mite allergen in vitro. The data may provide clues to the mechanism by which a number of LTRA including zafirulukast and montelukast can reduce airway, sputum and blood eosinophil counts in clinical asthma. It supports animal studies showing that anti-IL-5 antibodies partially block cys-LT-induced airway eosinophilia, suggesting that cys-LTs may cause secondary release of IL-5 from an unknown cell-type. These findings indicate that ONO-1078 suppresses the production of IL-4 (a cytokine that affects IgG antibody production), IL-5, and GM-CSF ( cytokines that affect eosinophil activation) by peripheral blood mononuclear cells under stimulation with specific antigens in patients with bronchial asthma. Because of its anti-inflammatory effects, ONO-1078 should be useful in the treatment of bronchial asthma.
|
Authors | Y Tohda, H Nakahara, H Kubo, R Haraguchi, M Fukuoka, S Nakajima |
Journal | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
(Clin Exp Allergy)
Vol. 29
Issue 11
Pg. 1532-6
(Nov 1999)
ISSN: 0954-7894 [Print] England |
PMID | 10520082
(Publication Type: Journal Article)
|
Chemical References |
- Chromones
- Cytokines
- Leukotriene Antagonists
- pranlukast
|
Topics |
- Adult
- Animals
- Asthma
(drug therapy, immunology)
- Chromones
(pharmacology)
- Cytokines
(biosynthesis, drug effects)
- Female
- Humans
- Hypersensitivity
(etiology)
- Leukocytes, Mononuclear
(drug effects, immunology)
- Leukotriene Antagonists
(pharmacology)
- Male
- Middle Aged
- Mites
(immunology)
|