Dual targeting of CCR2 and CCR5: therapeutic potential for immunologic and cardiovascular diseases.
A cardinal feature of inflammation is the tissue recruitment of leukocytes, a process that is mediated predominantly by chemokines via their receptors on migrating cells. CCR2 and CCR5, two CC chemokine receptors, are important players in the trafficking of monocytes/macrophages and in the functions of other cell types relevant to disease pathogenesis. This review provides a brief overview of the biological actions of CCR2 and CCR5 and a comprehensive summary of published data that demonstrate the involvement of both receptors in the pathogenesis of immunologic diseases (RA, CD, and transplant rejection) and cardiovascular diseases (atherosclerosis and AIH). In light of the potential for functional redundancy of chemokine receptors in mediating leukocyte trafficking and the consequent concern over insufficient efficacy offered by pharmacologically inhibiting one receptor, this review presents evidence supporting dual targeting of CCR2 and CCR5 as a more efficacious strategy than targeting either receptor alone. It also examines potential safety issues associated with such dual targeting.
Zhao
Qihong
Q
Research and Development, Bristol-Myers Squibb, Princeton, New Jersey 08543, USA. qihong.zhao@bms.com
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000209:etiology; D050197:Atherosclerosis / Q000188:drug therapy; D065100:CCR5 Receptor Antagonists; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy / Q000209:etiology; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D006965:Hyperplasia; D007154:Immune System Diseases / Q000188:drug therapy*; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D019713:Receptors, CCR5 / Q000502:physiology; D017539:Tunica Intima / Q000473:pathology
D065100:CCR5 Receptor Antagonists; D054390:Receptors, CCR2; D019713:Receptors, CCR5