Primer on the Rheumatic Diseases, 12th edition Order Your Copy Today!

Volume 51, Number 7

William P. Arend, MD
Division of Rheumatology
University of Colorado School of Medicine
Denver, CO

• Levels of IL-1 and TNF-a are increased in RA and allow migration of WBCs into inflammatory sites and the release of MMPs, which increase the inflammation and tissue damage.

• Etanercept and infliximab -- agents that block TNF-a -- result in clinical improvement in RA and limit bony damage.
• Anakinra, an IL-1 receptor antagonist, also results in clinical improvement of RA and limits bony damage.

Cytokines are small molecular weight proteins that mediate communication between cells (1,2). The generic term “cytokines” includes colony-stimulating factors, growth factors, interleukins, and interferons.

Cytokines carry out their functions primarily in the immediate cell environment in tissues, although some cytokines may act at a distance by traveling through the bloodstream. Cytokines work by binding to specific receptors on target cell surfaces, stimulating responses in cells that result in the increased or decreased production of proteins.

Cytokines are involved as mediator molecules in normal biologic processes. These physiologic functions include growth and differentiation of hematopoietic, lymphoid, and mesenchymal cells, as well as orchestration of host defense mechanisms.

Cytokines act in a self-regulatory network that is intended to maintain homeostasis of the internal environment. However, the unregulated or inappropriate production of particular cytokines may lead to pathological consequences in autoimmune and inflammatory diseases (3,4).

The inhibition of production or effects of specific cytokines has reached the therapeutic marketplace. The objective of this brief review is to present the background on tumor necrosis factor alpha (TNF-a) and interleukin-1 (IL-1) in rheumatoid arthritis (RA) and to summarize the results of clinical trials on new therapeutic approaches to block these cytokines.