CHEMOKINES - STRUCTURE, RECEPTORS AND FUNCTIONS - A NEW TARGET FOR INFLAMMATION AND ASTHMA THERAPY

FIVE to 10% Of the human population have a disorder of the respiratory tract called 'asthma'. It has been known as a potentially dangerous d isease for over 2000 years, as it was already described by Hippocrates and recognized as a disease entity by Egyptian and Hebrew physicians. At the beginning of this decade, there has been a fundamental change in asthma management. The emphasis has shifted from symptom relief wit h bronchodilator therapies (e.g. beta(2)-agonists) to a much earlier i ntroduction of antiinflammatory treatment (e.g. corticosteroids). Asth ma is now recognized to be a chronic inflammatory disease of the airwa ys, involving various inflammatory cells and their mediators. Although asthma has been the subject of many investigations, the exact role of the different inflammatory cells has not been elucidated completely. Many suggestions have been made and several cells have been implicated in the pathogenesis of asthma, such as the eosinophils, the mast cell s, the basophils and the lymphocytes. To date, however, the relative i mportance of these cells is not completely understood. The cell type p redominantly found in the asthmatic lung is the eosinophil and the rec ruitment of these eosinophils can be seen as a characteristic of asthm a. In recent years much attention is given to the role of the newly id entified chemokines in asthma pathology. Chemokines are structurally a nd functionally related 8-10 kDa peptides that are the products of dis tinct genes clustered on human chromosomes 4 and 17 and can be found a t sites of inflammation. They form a superfamily of proinflammatory me diators that promote the recruitment of various kinds of leukocytes an d lymphocytes. The chemokine superfamily can be divided into three sub groups based on overall sequence homology. Although the chemokines hav e highly conserved amino acid sequences, each of the chemokines binds to and induces the chemotaxis of particular classes of white blood cel ls. Certain chemokines stimulate the recruitment of multiple cell type s including monocytes, lymphocytes, basophils, and eosinophils, which are important cells in asthma Intervention in this process, by the dev elopment of chemokine antagonists, might be the key to new therapy. In this review we present an overview of recent developments in the fiel d of chemokines and their role in inflammations as reported in literat ure.