Successes and failures of chemokine-pathway targeting in rheumatoid arthritis

Z. Szekanecz, Alisa E. Koch

Research output: Contribution to journalArticle

61 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5-13
Number of pages9
JournalNature Reviews Rheumatology
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

ASJC Scopus subject areas

  • Rheumatology

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