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Int. J. Mol. Sci. 2015, 16(1), 887-906; doi:10.3390/ijms16010887

Cytokine-Modulating Strategies and Newer Cytokine Targets for Arthritis Therapy

Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: Bing Yan
Received: 10 November 2014 / Accepted: 25 December 2014 / Published: 31 December 2014
(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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Abstract

Cytokines are the key mediators of inflammation in the course of autoimmune arthritis and other immune-mediated diseases. Uncontrolled production of the pro-inflammatory cytokines such as interferon-γ (IFN-γ), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and IL-17 can promote autoimmune pathology, whereas anti-inflammatory cytokines including IL-4, IL-10, and IL-27 can help control inflammation and tissue damage. The pro-inflammatory cytokines are the prime targets of the strategies to control rheumatoid arthritis (RA). For example, the neutralization of TNFα, either by engineered anti-cytokine antibodies or by soluble cytokine receptors as decoys, has proven successful in the treatment of RA. The activity of pro-inflammatory cytokines can also be downregulated either by using specific siRNA to inhibit the expression of a particular cytokine or by using small molecule inhibitors of cytokine signaling. Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists delivered via gene therapy has proven to be an effective approach to regulate autoimmunity. Unexpectedly, under certain conditions, TNFα, IFN-γ, and few other cytokines can display anti-inflammatory activities. Increasing awareness of this phenomenon might help develop appropriate regimens to harness or avoid this effect. Furthermore, the relatively newer cytokines such as IL-32, IL-34 and IL-35 are being investigated for their potential role in the pathogenesis and treatment of arthritis. View Full-Text
Keywords: autoimmunity; arthritis; biologics; cytokines; gene therapy; inflammation; interleukins; rheumatoid arthritis; siRNA autoimmunity; arthritis; biologics; cytokines; gene therapy; inflammation; interleukins; rheumatoid arthritis; siRNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Venkatesha, S.H.; Dudics, S.; Acharya, B.; Moudgil, K.D. Cytokine-Modulating Strategies and Newer Cytokine Targets for Arthritis Therapy. Int. J. Mol. Sci. 2015, 16, 887-906.

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