Nerve growth factor expression and release in allergic inflammatory disease of the upper airways

It is well known that allergic airways disease is characterized by inflamma tion and hyperresponsiveness, but the link between these two conditions has not been elucidated. We have previously shown that in allergic rhinitis, h yperresponsiveness is attributable to increased neural reactivity. We thus hypothesized that nerve growth factor (NGF), which is expressed by inflamma tory 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 ev aluate NGF expression and release, we found that subjects with allergic rhi nitis have significantly decreased NGF mRNA in superficial nasal scrapings and significantly higher baseline concentrations of NGF protein in nasal la vage fluids, compared with control subjects. Nasal provocation with allerge n significantly increased NGF protein in nasal lavage fluids of subjects wi th allergic: rhinitis, but not of control subjects. The concentrations of N GF protein in nasal lavage fluids were not affected by provocation with the vehicle for allergen or with histamine. These data provide the first evide nce of a steady state of dysregulation in mucosal NGF expression and releas e in allergic rhinitis, and support a role of this neurotrophin in the path ophysiology of allergic inflammatory disease of the human airways.