Authors: Okamoto, Hiroshi; Hoshi, Daisuke; Kiire, Akiko; Yamanaka, Hisashi; Kamatani, Naoyuki

Source: Inflammation & Allergy - Drug Targets, Volume 7, Number 1, March 2008 , pp. 53-66(14)

Publisher: Bentham Science Publishers

Abstract:

Rheumatoid arthritis (RA) is a multifactorial disease characterized by chronic inflammation of the joints. Both genetic and environmental factors are involved in the pathogenesis of joint destruction and disability. In the inflamed RA joint, the synovium is highly infiltrated by CD4+ T cells, B cells, and macrophages. Furthermore, the intimal lining becomes hyperplastic due to the increased numbers of macrophage-like and fibroblast-like synoviocytes. This hyperplastic intimal synovial lining forms an aggressive front, called pannus, which invades cartilage and bone structures, leading to compromised function and/or destruction of affected joints. RA pathology is mediated by a number of cytokines (TNF-α, IL-1, IL-6, IL-17, IFNγ, etc.), chemokines (MCP-1, MCP-4, CCL18, etc.), cell adhesion molecules (ICAM-1, VCAM-1, etc.) and matrix metalloproteinases. Currently, treatment strategies targeted against TNF-α, IL-1 and IL-6 are available. In this review, we will summarize the use of biologics, the pros and cons of the use of biologics, and discuss on the potential molecular targets of RA.

Keywords: Tumor Necrosis Factor alpha; human anti-chimeric antibody; Interleukin-1; methotrexate; rituximab; Chemokines

Document Type: Research article

Publication date: 2008-03-01

More about this publication?

• Inflammation & Allergy - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in inflammation and allergy e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in inflammation and allergy. As the discovery, identification, characterization and validation of novel human drug targets for anti-inflammation and allergy drug discovery continues to grow, this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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