The role of neurotrophins in allergic bronchial asthma

Neurotrophins are known as target-derived factors regulating the development, survival and function of distinct neuronal subsets. This family of structurally related growth factors includes nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4. Beyond their originally described effects on neurones, neurotrophins are involved in many other biological processes including immune regulation, smooth muscle differentiation and neuroendocrine functions. The pathogenesis of allergic bronchial asthma is characterized by a complex interaction between inflammatory, epithelial, smooth muscle cells and neurones. This results in the development of airway inflammation, airway obstruction, airway hyperresponsiveness and airway remodelling. The altered neuronal control of airway smooth muscle tone is a hallmark in bronchial asthma. Growing evidence suggests that T cells, B cells, macrophages and mast cells produce high quantities of neurotrophic factors during allergic inflammation. Therefore, they are likely candidates as mediators between allergic inflammation and airway hyperresponsiveness. Neurotrophins increase excitability and neurotransmitter synthesis in sensory neurones and can also affect motor neurones. They enhance local neuropeptide release and augment central reflexes. Additionally, neurotrophins can affect immune functions and smooth muscle physiology. Therefore, neurotrophins are involved in the cellular communication between different compartments of the asthmatic lung. Delineating the mechanisms of this cross-talk will give new insights into the pathogenesis of asthma.