Nerve growth factor and asthma

Increasing evidence accumulated from research performed in our own and other laboratories - and briefly reviewed below - indicates that the role of nerve growth factor (NGF) is not confined to the central and peripheral nervous system, but also extends to allergic diseases and asthma. (I) NGF serum levels are increased in patients with allergic diseases and asthma and related to the severity of the inflammatory process and disease. In vernal keratoconjunctivitis, NGF plasma levels correlate with the number of mast cells infiltrating the conjunctiva and with circulating levels of substance P. In a mouse model of allergic airway inflammation and asthma, an increased number of NGF-positive cells was detectable in the inflammatory infiltrate of the lung, and increased levels of NGF were present in serum and bronchoalveolar lavage fluids. In humans. increased mRNA for NGF is found in nasal mucosal scrapings of patients with allergic rhinitis who also show high levels of NGF in serum and nasal fluids, further increasing after specific allergen challenge. (2) NGF is released by several modulatory and effector cells of allergic inflammation and asthma, such as Th2 CD4 positive cells, mast cells, and eosinophils. NGF also increases airway hyperreactivity to histamine in a guinea pig model of asthma. (3) NGF receptors are expressed on epithelial cells of patients with allergic conjunctivitis as well as several inflammatory cells. These are able to respond to NGF with activation and mediator release. NGF administration to the eye in humans has a profound effect on fibroblast activation and reparative processes of corneal ulcers. suggesting a role for NGF also in tissue remodelling processes occurring in asthma. (4) In the mouse, anti-NGF treatment reduces airways hyperreactivity induced by ovalbumin topical challenge of sensitized animals. The above data strongly suggest that NGF is an important mediator in allergic diseases and asthma.