Biology of Neurotrophins, Neuropeptides, and Muscarinic Receptors in Asthma

Asthma is a chronic respiratory disorder involving clinical features like bronchoconstriction, mucus production and airway hyperreactivity. The mechanisms responsible for these effects are diverse and still not understood. Airway inflammation and alterations in neuronal function are thought to play a key role, which go hand in hand in mediating the full blown disease. Neurotrophins like nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4) have been identified to be involved in neuroimmune crosstalks in allergic diseases like atopic dermatitis and asthma. The NGF overexpressing mice (CCSP-NGFtg) are hyperinnervated and show an increased AHR upon allergen challenge. Neuropeptides like substance P (SP) and tachykinins have also increasingly been reported to mediate immunological modulations in asthma. The neurotrophins and neuropeptides closely interact with each other and the outcome of disease could be a result of their mutual interaction. Asthmatic patients are known to be sensitive to a number of bronchoconstrictor agents like bradykinin, sulfur dioxide, distilled water, adenosine, and capsaicin whereas healthy individuals are not. A common feature in these exposure and stimulations is the indirect stimulation of airway nerves thereby affecting changes in lung function. The parasympathetic nervous system is the dominant neuronal pathway of airway smooth muscle tone. Stimulation of cholinergic nerves causes bronchoconstriction, mucus secretion, and bronchial vasodilatation. The following chapter describes the role of the above mentioned mediators and their direct and/or indirect involvement in neuro-immune interactions in allergic diseases, especially asthma.