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Cytokine-modulating strategies and newer cytokine targets for arthritis therapy.

Venkatesha SH, Dudics S, Acharya B, Moudgil KD - Int J Mol Sci (2014)

Bottom Line: Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists delivered via gene therapy has proven to be an effective approach to regulate autoimmunity.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 Article: PubMed Central - PubMed

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.

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.

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Related in: MedlinePlus

Diverse strategies employed to control the activity of pro-inflammatory cytokines and tissue damage. Pro-inflammatory cytokines, when produced in excess, can cause significant damage to tissues in various autoimmune diseases. Multiple approaches have been developed to prevent and ameliorate the harmful side effects of the pro-inflammatory cytokines. Anti-cytokine antibodies can inhibit the binding of the cytokines to their receptors. Decoy receptors can similarly bind the cytokines and prevent them from binding to the corresponding natural receptors on the cell surface. Gene therapy can be used to suppress the production of specific pro-inflammatory cytokines, whereas siRNAs can silence particular mRNA that encode the cytokine and thereby, prevent its production. Small molecule inhibitors can target certain pathways involved in the production of pro-inflammatory cytokines as well as inhibit their signaling abilities. Finally, anti-inflammatory cytokines help downregulate the pathogenic immune responses and subsequently inhibit further tissue damage. Paradoxically, TNFα can display anti-inflammatory properties under certain conditions.
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ijms-16-00887-f002: Diverse strategies employed to control the activity of pro-inflammatory cytokines and tissue damage. Pro-inflammatory cytokines, when produced in excess, can cause significant damage to tissues in various autoimmune diseases. Multiple approaches have been developed to prevent and ameliorate the harmful side effects of the pro-inflammatory cytokines. Anti-cytokine antibodies can inhibit the binding of the cytokines to their receptors. Decoy receptors can similarly bind the cytokines and prevent them from binding to the corresponding natural receptors on the cell surface. Gene therapy can be used to suppress the production of specific pro-inflammatory cytokines, whereas siRNAs can silence particular mRNA that encode the cytokine and thereby, prevent its production. Small molecule inhibitors can target certain pathways involved in the production of pro-inflammatory cytokines as well as inhibit their signaling abilities. Finally, anti-inflammatory cytokines help downregulate the pathogenic immune responses and subsequently inhibit further tissue damage. Paradoxically, TNFα can display anti-inflammatory properties under certain conditions.

Mentions: In this article, we describe a variety of approaches used for modulation of cytokine responses to control arthritis (Figure 2, Table 1 and Table 2) and the properties of relatively newer cytokines (IL-32, IL-34, and IL-35), which have shown association with RA pathology and are being tested for their use in arthritis therapy in experimental models of RA.


Cytokine-modulating strategies and newer cytokine targets for arthritis therapy.

Venkatesha SH, Dudics S, Acharya B, Moudgil KD - Int J Mol Sci (2014)

Diverse strategies employed to control the activity of pro-inflammatory cytokines and tissue damage. Pro-inflammatory cytokines, when produced in excess, can cause significant damage to tissues in various autoimmune diseases. Multiple approaches have been developed to prevent and ameliorate the harmful side effects of the pro-inflammatory cytokines. Anti-cytokine antibodies can inhibit the binding of the cytokines to their receptors. Decoy receptors can similarly bind the cytokines and prevent them from binding to the corresponding natural receptors on the cell surface. Gene therapy can be used to suppress the production of specific pro-inflammatory cytokines, whereas siRNAs can silence particular mRNA that encode the cytokine and thereby, prevent its production. Small molecule inhibitors can target certain pathways involved in the production of pro-inflammatory cytokines as well as inhibit their signaling abilities. Finally, anti-inflammatory cytokines help downregulate the pathogenic immune responses and subsequently inhibit further tissue damage. Paradoxically, TNFα can display anti-inflammatory properties under certain conditions.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307281&req=5

ijms-16-00887-f002: Diverse strategies employed to control the activity of pro-inflammatory cytokines and tissue damage. Pro-inflammatory cytokines, when produced in excess, can cause significant damage to tissues in various autoimmune diseases. Multiple approaches have been developed to prevent and ameliorate the harmful side effects of the pro-inflammatory cytokines. Anti-cytokine antibodies can inhibit the binding of the cytokines to their receptors. Decoy receptors can similarly bind the cytokines and prevent them from binding to the corresponding natural receptors on the cell surface. Gene therapy can be used to suppress the production of specific pro-inflammatory cytokines, whereas siRNAs can silence particular mRNA that encode the cytokine and thereby, prevent its production. Small molecule inhibitors can target certain pathways involved in the production of pro-inflammatory cytokines as well as inhibit their signaling abilities. Finally, anti-inflammatory cytokines help downregulate the pathogenic immune responses and subsequently inhibit further tissue damage. Paradoxically, TNFα can display anti-inflammatory properties under certain conditions.
Mentions: In this article, we describe a variety of approaches used for modulation of cytokine responses to control arthritis (Figure 2, Table 1 and Table 2) and the properties of relatively newer cytokines (IL-32, IL-34, and IL-35), which have shown association with RA pathology and are being tested for their use in arthritis therapy in experimental models of RA.

Bottom Line: Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists delivered via gene therapy has proven to be an effective approach to regulate autoimmunity.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 Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus