CCR3 and CXCR3 as drug targets for allergy: principles and potential.
Atopic disorders include a range of conditions such as allergic asthma, -rhinitis, -conjunctivitis, -dermatitis, food and drug allergies and anaphylaxis. Induction of T helper (Th)-2 immune response with consequent IgE dependent eosinophil, basophil and mast cell mediated tissue damage is the characteristic feature of allergies. The mechanism underlying this unique and long appreciated feature of allergy is being elucidated at the molecular level with advances in our knowledge of the chemokine system. Thus, chemokines that target CCR3 in concert with Th2 cytokines appear to play a pathogenic role in allergy. In contrast, chemokines that target CXCR3 in concert with Th1 cytokine appear to play a beneficial role. Accordingly, inhibiting CCR3/Th2 pathway using CCR3 antagonists is viewed as a potentially useful strategy for anti-allergy drug development. In contrast, the idea of using CXCR3 agonists to inhibiting allergic response by promoting CXCR3/Th1 pathway faces serious concerns of their potential pro-inflammatory activities in vivo. In this article we have critically evaluated the literature examining the principle and potential of this anti-allergy drug development strategy including a summary of various compounds that are under investigation.
Gangur
Venu
V
Food Allergy and Immunology Laboratory, Michigan State University, East Lansing, MI 48824, USA. gangur@msu.edu
Birmingham
Neil P
NP
Thanesvorakul
Sirinart
S
Joseph
Shama
S
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D054397:Receptors, CCR3; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000276:immunology
C515350:CCR3 protein, human; C515187:CXCR3 protein, human; D018925:Chemokines; D054397:Receptors, CCR3; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine