Neurotrophins and asthma: Novel insight into neuroimmune interaction

There is increasing evidence that neuronal dysfunction and dysregulation contribute to the pathogenesis of allergic asthma. Many functional aspects of peripheral neurons strongly depend on the activity of neurotrophins, a family of mediators originally defined by their neuronal growth activity. More recently, it has been discovered that neurotrophins (eg, nerve growth factor, brain-derived neurotrophin factor, and neurotrophin 3) have profound activities on various immune cells involved in the pathogenesis of allergic disease. Furthermore, immune cells themselves can produce neurotrophins under certain conditions, and the levels of neurotrophins, as well as neurotrophic activities, are strongly upregulated in allergic conditions. Animal data demonstrate that a number of pathomechanisms controlling allergic diseases are directly related to neurotrophin function, including the development of airway hyperresponsiveness. These findings now lead to a much better understanding concerning the regulatory loop between immunologic and neurogenic dysregulation. In this review we will provide an overview of how neurotrophins connect the pathobiology of airway inflammation and hyperresponsiveness, which are the hallmarks of allergic asthma.

Key words: Asthma, allergy, neurotrophins, airway inflammation, airway hyperresponsiveness, neuroimmune interaction

Abbreviations used: AHR, Airway hyperresponsiveness, BALF, Bronchoalveolar fluid, BDNF, Brain-derived neurotrophic factor, NGF, Nerve growth factor, NT-3, Neurotrophin 3, NT-4/5, Neurotrophin 4/5, Trk, Tropomyosin-related tyrosine kinase