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Antibodies directed against nerve growth factor inhibit the acute bronchoconstriction due to allergen challenge in guinea‐pigs
Author(s) -
De Vries A.,
Engels F.,
Henricks P. A. J.,
LeusinkMuis T.,
Fischer A.,
Nijkamp F. P.
Publication year - 2002
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.2002.01283.x
Subject(s) - bronchoconstriction , guinea pig , immunology , allergen , medicine , nerve growth factor , antibody , asthma , allergy , receptor
BackgroundWe have previously demonstrated that the administration of nerve growth factor (NGF) to guinea‐pigs results in airway hyper‐responsiveness within 1 h. Objective In the present study we document the involvement of NGF in the acute allergic airway response. Methods Guinea‐pigs that are sensitized to ovalbumin show an acute bronchoconstriction directly after challenge with ovalbumin. Results Intratracheal application of 10 µg of antibodies directed against NGF (anti‐NGF) 1 h before the challenge reduces the acute severe bronchoconstriction to approximately 40% and the sustained bronchoconstriction to approximately 20% of the reaction in controls. This shows a high potency of anti‐NGF in diminishing the direct bronchoconstriction. Inhibition of the tyrosine kinases of the tyrosine kinase receptor A, the high‐affinity receptor for NGF, has no effect on the bronchoconstriction. Therefore, we postulate that the p75, the low‐affinity receptor for neurotrophins, is responsible for the acute bronchoconstriction. Our findings suggest a role for NGF in the induction of the acute asthmatic reaction. Conclusion These findings offer a new potential therapeutic strategy for the treatment of allergic asthma.