Chemokine receptors and their antagonists in allergic lung disease.
The trafficking and homing of leukocytes in normal homeostasis and in disease is under the control of a variety of cytokine and lipid mediators. One family of small cytokines particularly involved in inflammation which has been identified is the chemokine family. Their action is mediated by a large superfamily of seven transmembrane spanning G-protein coupled receptors. One of the hopes in this field has been there may be selectivity in terms of which cells are recruited to sites of inflammation by virtue of their chemokine receptor expression pattern. This means that it may be possible to find antagonists of chemokine receptors that can selectively down regulate certain cell type recruitment, without provoking a generalized immunosuppression. In this review, we discuss the current state of understanding of the chemokine receptor field. The therapeutic potential of this field can be judged from recent data on the use of protein chemokine antagonists in allergic disease. The data so far obtained in animal studies point to the potential clinical uses of this emerging class of therapeutic agents.
Wells
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Serono Pharmaceutical Research Institute, Geneva, Switzerland. tim.wells@serono.com
Proudfoot
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AE
D001249:Asthma / Q000188:drug therapy* / Q000209:etiology; D001327:Autoimmune Diseases / Q000276:immunology; D018925:Chemokines / Q000502:physiology; D006025:Glycosaminoglycans / Q000502:physiology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology
D018925:Chemokines; D006025:Glycosaminoglycans; D019707:Receptors, Chemokine