Nerve Growth Factor Expression and Release in Allergic Inflammatory Disease of the Upper Airways

Abstract

It is well known that allergic airways disease is characterized by inflammation and hyperresponsiveness, but the link between these two conditions has not been elucidated. We have previously shown that in allergic rhinitis, hyperresponsiveness is attributable to increased neural reactivity. We thus hypothesized that nerve growth factor (NGF), which is expressed by inflammatory cells and effects changes that lead to increased neural responsiveness, could be a pivotal mediator in this disease. Using reverse transcription-polymerase chain reaction (RT-PCR), Western immunoblotting, and ELISA to evaluate NGF expression and release, we found that subjects with allergic rhinitis have significantly decreased NGF mRNA in superficial nasal scrapings and significantly higher baseline concentrations of NGF protein in nasal lavage fluids, compared with control subjects. Nasal provocation with allergen significantly increased NGF protein in nasal lavage fluids of subjects with allergic rhinitis, but not of control subjects. The concentrations of NGF protein in nasal lavage fluids were not affected by provocation with the vehicle for allergen or with histamine. These data provide the first evidence of a steady state of dysregulation in mucosal NGF expression and release in allergic rhinitis, and support a role of this neurotrophin in the pathophysiology of allergic inflammatory disease of the human airways.

Local Effect of Neurotrophin-3 in Neuronal Inflammation of Allergic Rhinitis: Preliminary Repor

“…These findings suggest that activation of neurotrophins may be an alternative pathway in AR pathogenesis. In our study, we found that NT-3 staining levels of nasal mucosa were higher in the AR group than in the control group; this finding is similar to the literature regarding other neurotrophins (2,16,22) Increases in serum neurotrophin levels in allergic diseases has also been shown (12,16), whereas, in the study of Raap et al (16), this increase was not statistically significant both before and after nasal provocation tests. Furthermore, it is also known that neurotrophins have autocrine or paracrine features.…”

“…It has been shown that NGF levels of nasal lavage fluid were higher (22) and NGF and BDNF were overexpressed in nasal tissue of AR patients (16). Raap et al (23) showed that eosinophil apoptosis is inhibited when eosinophils are stimulated by NT-3.…”

Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper

“…The molecular mechanisms of hyperresponsiveness are not understood, but several inflammatory products appear to play a role. Neurotrophins, such as the nerve growth factor (122), are prime candidates for mediators of neural hyperresponsiveness.…”

Inflammation-Induced Plasticity of the Afferent Innervation of the Airways

“…Among the family of neurotrophins most attention has been given to NGF as a potential mediator in afferent plasticity in inflamed airways. NGF is found in human airways, and the NGF content of airway lavage fluid is increased following allergen challenge (61,(64)(65)(66). NGF is capable of regulating the expression of mRNAs encoding the precursors of substance P and CGRP in mature afferent neurons (67).…”