title: Successes and failures of chemokine-pathway targeting in rheumatoid arthritis.
abstract: Chemokines and chemokine receptors are involved in leukocyte recruitment and angiogenesis underlying the pathogenesis of rheumatoid arthritis (RA) and other inflammatory rheumatic diseases. Numerous chemokines, along with both conventional and atypical cell-surface chemokine receptors, are found in inflamed synovia. Preclinical studies carried out in animal models of arthritis involving agents targeting chemokines and chemokine receptors have yielded promising results. However, most human trials of treatment of RA with antibodies and synthetic compounds targeting chemokine signalling have failed to show clinical improvements. Chemokines can have overlapping actions, and their activities can be altered by chemical modification or proteolytic degradation. Effective targeting of chemokine pathways must take acount of these properties, and can also require high levels of receptor occupancy by therapeutic agents to prevent signalling. CCR1 is a promising target for chemokine-receptor blockade.
authors.affiliation: Department of Rheumatology, Institute of Medicine, University of Debrecen Faculty of Medicine, Nagyerdei Str 98, Debrecen, H-4004, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szekanecz
authors.affiliation: University of Michigan Health System, Department of Internal Medicine, Division of Rheumatology, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Koch
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D018925:Chemokines / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D018925:Chemokines; D007155:Immunologic Factors