Effect of thromboxane A2 antagonists on bronchial hyperresponsiveness induced immediately after interleukin-8 inhalation in guinea-pigs.
1. Although repeated intranasal administration of interleukin-8 (IL-8) causes bronchial hyperresponsiveness (BHR) mediated via thromboxane A2 (TXA2) 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 TXA2. 2. The effects of inhaled IL-8 on bronchial responsiveness and of the TXA2 antagonists, S-1452 (0.01 and 0.1 mg kg-1) and ONO-NT-126 (1.0 or 10 micrograms 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 micrograms 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 TXA2 release in guinea-pigs.
Fujimura
M
M
Third Department of Internal Medicine, Kanazawa University School of Medicine, Ishikawa, Japan.
Myou
S
S
Nomura
M
M
Matsuda
T
T
Harada
A
A
Mukaida
N
N
Matsushima
K
K
Nonomura
A
A
D000280:Administration, Inhalation; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006168:Guinea Pigs; D016209:Interleukin-8 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D016593:Terfenadine / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D016209:Interleukin-8; D011448:Prostaglandin Antagonists; C056566:S 145; D013928:Thromboxane A2; D016593:Terfenadine