title: Cytokine-modulating strategies and newer cytokine targets for arthritis therapy.
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.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA. hvshivaprasad@gmail.com.
authors.forename: Shivaprasad H
authors.initials: SH
authors.lastname: Venkatesha
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA. sdudics1@gmail.com.
authors.forename: Steven
authors.initials: S
authors.lastname: Dudics
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA. bacharya@som.umaryland.edu.
authors.forename: Bodhraj
authors.initials: B
authors.lastname: Acharya
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA. kmoud001@umaryland.edu.
authors.forename: Kamal D
authors.initials: KD
authors.lastname: Moudgil
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007166:Immunosuppressive Agents; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha