Antibodies directed against nerve growth factor inhibit the acute bronchoconstriction due to allergen challenge in guinea-pigs.
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.


CONCLUSIONS
These findings offer a new potential therapeutic strategy for the treatment of allergic asthma.
De Vries
A
A
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, the Netherlands. G.M.H.Engels@pharm.uu.nl
Engels
Ferdi
F
Henricks
P A J
PA
Leusink-Muis
T
T
Fischer
A
A
Nijkamp
F P
FP
D000208:Acute Disease; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use*; D001986:Bronchial Spasm / Q000188:drug therapy* / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006168:Guinea Pigs; D008297:Male; D020932:Nerve Growth Factor / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014132:Trachea; D020032:Tyrphostins / Q000627:therapeutic use
C081020:AG-879; D000485:Allergens; D000906:Antibodies; D004791:Enzyme Inhibitors; D020032:Tyrphostins; D010047:Ovalbumin; D020932:Nerve Growth Factor; D011505:Protein-Tyrosine Kinases