Am. J. Respir. Crit. Care Med., Volume 161, Number 5, May 2000, 1631-1635

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

ALVIN M. SANICO, ANDRZEJ M. STANISZ, TODD D. GLEESON, SUSAN BORA, DAVID PROUD, JOHN BIENENSTOCK, VASSILIS E. KOLIATSOS, and ALKIS TOGIAS

Department of Medicine, Division of Clinical Immunology, and Department of Medicine, Division of Respiratory and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Pathology, Division of Neuropathology, Department of Neurology, Department of Neuroscience, and Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland

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.

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