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IL‐1 mediates persistent but not acute ozone‐induced airway hyperreactivity
Author(s) -
Blensly Kirsten Colleen,
Jacoby David B,
Fryer Allison D
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.764.11
Subject(s) - bronchoconstriction , medicine , antagonist , bronchoalveolar lavage , eosinophil , immunology , endocrinology , airway , anesthesia , receptor , asthma , lung
Ozone (O3) exposure causes airway hyperreactivity, lasting at least 3 days, and increases interleukin‐1 (IL‐1) in human and animal lungs. Eosinophil depletion prevents O3 induced airway hyperreactivity 1 day post O3 but worsens airway hyperreactivity 3 days post O3. Thus, the mechanism of hyperreactivity changes between 1 and 3 days following O3 exposure in guinea pigs. O3 increases IL‐1a in bone marrow. To test whether IL‐1β mediates airway hyperreactivity 1 and 3 days post O3 guinea pigs were treated with an IL‐1 receptor antagonist (Kineret, 30mg/kg ip) 30 minutes before exposure to filtered air or O3 (2ppm, 4 hours). One or 3 days later electrical stimulation of both vagus nerves, in anesthetized animals, caused bronchoconstriction that was significantly potentiated in O3 exposed animals compared to air exposed controls. The IL‐1 antagonist prevented airway hyperreactivity 3 days but not 1 day post O3. Acetylcholine (1‐10ug/kg, iv) induced bronchoconstriction was not changed 1 or 3 days post O3 but was increased in O3 exposed animals treated with the IL‐1 antagonist. In bronchoalveolar lavage the IL‐1 antagonist did not change inflammatory cell numbers in either O3 or air exposed animals at either time point. These data confirm the mechanism of airway hyperreactivity changes over three days following ozone to become IL‐1 dependent. Funding: Steinberg Fellowship; NIH: HL‐55543, HL54659, HL071795 , ES‐014601