Ž . International Immunopharmacology 1 2001 1629–1650 www.elsevier.comrlocaterintimp Review Tachykinins and neuro-immune interactions in asthma A.D. Kraneveld ) , F.P. Nijkamp Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht UniÕersity, P.O. Box 80082, 3508 TB Utrecht, The Netherlands Received 8 December 2000; received in revised form 11 May 2001; accepted 23 May 2001 Abstract Excitatory non-adrenergic–non-cholinergic neuropeptides, such as the tachykinins substance P and neurokinin A, and its receptors are present in human and animal airways. Tachykinins are biologically active at extremely low concentrations. These peptides can cause potent inflammatory effects and can affect airway function in a way that resembles features of Ž . asthma. Local release of tachykinins affects blood vessels vasodilatation and increased vascular permeability and bronchial Ž . smooth muscle bronchoconstrition and hyperresponsiveness . Neuropeptide research has revealed that tachykinins also play an important modulatory role in immune reactions. Tachykinins stimulate immune cells, such as mast cells, lymphocytes, and macrophages and are chemotactic for neutrophils and eosinophils. Vice versa, a range of immune cell mediators can also induce the release of tachykinins from excitatory NANC nerve endings in the airways. In the last 20 years, significant advances have been made in investigations of the interaction between immune cells and nervous systems in chronic inflammatory diseases such as asthma. q 2001 Elsevier Science B.V. All rights reserved. Ž . Keywords: Asthma; NANC non-adrenergic–non-cholinergic nerves; Tachykinins; Immune cells; Animal model; Human 1. Introduction Asthma is characterised by episodic reversible airway obstruction along with bronchial hyperre- sponsiveness and airway inflammation. Bronchial asthma can be subdivided into an allergic and a nonallergic form, although the two forms are not always strictly separated. The most obvious differ- ence between allergic and nonallergic asthma is the serum IgE levels, which are increased in allergic asthma, whereas no elevated IgE levels can be mea- ) Corresponding author. Tel.: q 31-30-253-4509; fax: q 31-30- 253-7420. E-mail address: A.D.Kraneveld@pharm.uu.nl Ž . A.D. Kraneveld . sured in subjects with nonallergic asthma. A com- mon feature in both groups of asthmatic patients is a significant involvement of inflammatory cells, either pulmonary tissue resident, such as macrophages and mast cells, or infiltrated inflammatory cells, such as eosinophils, neutrophils and lymphocytes. In addi- tion, tissue resident structural cells, such as epithelial cells, smooth muscle cells, endothelial cells and fibroblasts, may also be an important source for inflammatory mediators in asthma. These sources could be important in persisting the asthmatic in- flammatory process in absence of activating stimuli. Human airways are innervated by efferent and afferent autonomic nerves which regulate many as- w x pects of airway function 1–3 . Neuronal control of airways may be abnormal in asthmatic patients and neurogenic mechanisms contribute to the pathogene- 1567-5769r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. Ž . PII: S1567-5769 01 00099-6