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Effect of thromboxane A 2 antagonists on bronchial hyperresponsiveness induced immediately after interleukin‐8 inhalation in guinea‐pigs
Author(s) -
Fujimura Masaki,
Myou Shigeharu,
Nomura Masaharu,
Matsuda Tamotsu,
Harada Akihisa,
Mukaida Naofumi,
Matsushima Kouji,
omura Akitaka
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701478
Subject(s) - bronchial hyperresponsiveness , methacholine , medicine , inhalation , histamine , guinea pig , thromboxane , airway resistance , asthma , pharmacology , nasal administration , thromboxane a2 , immunology , anesthesia , lung , platelet , respiratory disease
1 Although repeated intranasal administration of interleukin‐8 (IL‐8) causes bronchial hyperresponsiveness (BHR) mediated via thromboxane A 2 (TXA 2 ) and airway neutrophil accumulation in guinea‐pigs, the acute effect of inhaled IL‐8 is unclear. We performed this study to clarify the acute effect of IL‐8 on bronchial responsiveness and the role of TXA 2 . 2 The effects of inhaled IL‐8 on bronchial responsiveness and of the TXA 2 antagonists, S‐1452 (0.01 and 0.1 mg kg −1 ) and ONO‐NT‐126 (1.0 or 10 μg kg −1 ), on IL‐8‐induced BHR were examined by use of a modified Konzett‐Rössler method in guinea‐pigs. 3 Inhaled IL‐8 at 100 ng ml −1 , which failed to induce significant changes in Pao (pressure at the airway opening), enhanced an increase in Pao induced by subsequent inhalations of ascending doses (50–200 μg ml −1 ) of methacholine and histamine, suggesting the potentiating effect of IL‐8 on bronchial responsiveness. No significant leukocyte infiltration was observed histologically sixteen minutes after the IL‐8 inhalation. Both S‐1452 and ONO‐NT‐126 reduced the IL‐8‐induced BHR. 4 In conclusion, IL‐8 rapidly causes BHR via TXA 2 release in guinea‐pigs.British Journal of Pharmacology (1997) 122 , 1015–1020; doi: 10.1038/sj.bjp.0701478