Antibodies directed against nerve growth factor inhibit the acute bronchoconstriction due to allergen challenge in guinea-pigs
de Vries, Annick × Engels, Ferdi Henricks, P A J Leusink-Muis, T Fischer, A Nijkamp, F P #
Blackwell Scientific Publications
Clinical and Experimental Allergy vol:32 issue:2 pages:325-328
BACKGROUND: We 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 microg 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.