Nerve growth factor induces a neurokinin-1 receptor-mediated airway hyperresponsiveness in guinea pigs

Because asthmatic patients show increased nerve growth factor (NGF) serum l evels, we examined the effect of NGF on airway function. Intravenously admi nistered NGF potentiates the histamine-induced bronchoconstriction with a m aximum of over 200% in anesthetized spontaneously breathing guinea pigs, Do ses of 8 ng and 80 ng NGF/kg body weight induce a significant hyperresponsi veness to histamine. NGF itself does not affect airway reactivity, Airway h yperresponsiveness is observed 30 min and 3 h after NGF administration, and has disappeared after 24 h, The neurokinin-1 receptor antagonist SR 140333 completely blocks the NGF-induced hyperresponsiveness, pointing to a role for tachykinins. This is the first report showing a direct relation between peripherally administered NGF and airway hyperresponsiveness. Taking into consideration that plasma NGF levels have been shown to be elevated in asth matic patients, our result points to an important role for NGF in the patho genesis of asthma.