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Cytokine networks in rheumatic diseases: Implications for therapy

Author
Iain B McInnes, FRCP, PhD
Section Editor
Daniel E Furst, MD
Deputy Editor
Paul L Romain, MD

INTRODUCTION

Understanding the contribution of cytokines to the pathogenesis of rheumatic diseases offers novel and creative therapeutic options that were not previously available. This is especially true in rheumatoid arthritis (RA), in which the cytokine milieu of the joint is reasonably well-understood and in which data on human clinical trials are already available. Therapies designed to block the effects of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 receptor (IL-6R) action in this illness are effective in many patients with RA, as are TNF inhibitors and IL-17A inhibitors in psoriatic arthritis. (See "Overview of biologic agents and kinase inhibitors in the rheumatic diseases".)

Although biologic agents that regulate cytokines have met with success in the treatment of RA and other inflammatory arthropathies, small molecules that block cytokine production and/or signaling may have a competitive advantage in the coming years. An important note of caution, however, is that there is the possibility that suppressing even physiologic concentrations of some cytokines could have serious adverse effects on immune surveillance.

This topic will review the issues relating to the manipulation of cytokine networks in patients with rheumatic disease, with an emphasis on RA. The pathogenesis of RA is discussed separately. (See "Pathogenesis of rheumatoid arthritis".)

INHIBITION OF CYTOKINE PRODUCTION

A host of biologic and small molecules with anticytokine properties are being developed or are already in clinical use.

Glucocorticoids — Glucocorticoids (eg, prednisone, prednisolone, or triamcinolone), which are potent transcriptional inhibitors of production of a variety of cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF), have been available for many years and have clear utility in rheumatic disorders. It is not certain whether this activity accounts for their therapeutic benefit or, more likely, whether it represents only one of many effects of glucocorticoids. Other activities that might be therapeutically important include the inhibition of adhesion molecule expression, arachidonic acid metabolism, and metalloproteinase production. These and other effects of glucocorticoids on the immune system are discussed in more detail elsewhere. (See "Glucocorticoid effects on the immune system".)

                                            

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Literature review current through: Nov 2016. | This topic last updated: Mon Oct 17 00:00:00 GMT+00:00 2016.
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