Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin-8 in guinea-pigs in vivo.
BACKGROUND
Interleukin-8 (IL-8) has been shown to be a chemotactic factor for neutrophils, T-lymphocytes and eosinophils. Repeated intranasal administration of IL-8 enhances bronchial responsiveness to inhaled histamine in guinea-pigs. Neuropeptides which are released from C-fibre nerve-endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation.


OBJECTIVE
This study was conducted to examine whether sensory neuropeptides are involved in the IL-8-induced bronchial hyperresponsiveness.


METHODS
IL-8 at a dose of 5 micrograms/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilated through tracheal cannula, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses to increasing concentrations of inhaled histamine (25, 50, 100, and 200 micrograms/mL). A NK1 and NK2 dual antagonist FK224 (10 mg/kg), a selective NK1 antagonist FK888 (10 mg/kg) or vehicle was intravenously administered 10 min before measurement of bronchial responsiveness.


RESULTS
The IL-8 treatment significantly enhanced bronchial responsiveness to histamine (ANOVA P < 0.01). FK224 or FK888 did not alter the IL-8-induced bronchial hyperresponsiveness.


CONCLUSIONS
We conclude that repeated intranasal administration of IL-8 causes bronchial hyperresponsiveness (BHR) and that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of BHR induced by IL-8.
Fujimura
M
M
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Tsujiura
M
M
Nomura
M
M
Mizuguchi
M
M
Matsuda
T
T
Matsushima
K
K
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000188:drug therapy; D001985:Bronchial Provocation Tests; D004151:Dipeptides / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage / Q000009:adverse effects; D007211:Indoles / Q000494:pharmacology*; D016209:Interleukin-8 / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D015288:Neurokinin A / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism
D004151:Dipeptides; D007211:Indoles; D016209:Interleukin-8; D010456:Peptides, Cyclic; C075570:FK 224; C078949:FK 888; D013373:Substance P; D006632:Histamine; D015288:Neurokinin A