Inhibition of IL6 in rheumatoid arthritis and juvenile idiopathic arthritis.
ABSTRACT A number of clinical trials have been done to investigate the role of interleukin-6 (IL-6) as a potential therapeutic target in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Most of the data testing this comes from trials of the humanized anti Il-6 receptor antibody tocilizumab. Results from clinical trials worldwide have been promising so far. Additional study will define the ultimate role of tocilizumab and Il6 inhibitors in the treatment paradigms for RA and JIA.
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ABSTRACT: Small hyaluronan (HA) fragments produced from native HA during inflammation contribute greatly to cell injury in many pathologies. HA oligosaccharides increase proinflammatory cytokine levels by activating both CD44 and toll-like receptor (TLR)-4. Stimulation of CD44 and TLR-4 then activates nuclear factor-κB, which induces the production of proinflammatory cytokines. The adenosine 2A receptor (A(2A)R) is also involved in several inflammation pathologies, and the nucleoside adenosine acts as a potent endogenous inhibitor of inflammation in various tissues by interacting with this receptor. The aim of this study was to investigate the effects of an HA-blocking peptide that inhibits the proinflammatory action of HA oligosaccharides produced during inflammation, together with a specific A(2A)R agonist in a model of normal mouse articular chondrocytes stimulated with interleukin (IL)-1β. IL-1β stimulation significantly increased mRNA expression and the related protein production of TLR-4, TLR-2, CD44 and A(2A)R in articular chondrocytes. The induced nuclear factor-κB activation was also associated with increased levels of inflammatory cytokines, including tumor necrosis factor-α and IL-6, and other inflammatory mediators, such as matrix metalloprotease-13 and inducible nitric oxide synthase. Treatment of chondrocytes with the HA-blocking peptide Pep-1 and/or a specific A(2A)R agonist (CGS-21680) significantly reduced all of the inflammatory parameters upregulated by IL-1β. These results suggest that the inflammatory response may be reduced either by blocking oligosaccharides from HA degradation or by A(2A)R stimulation.FEBS Journal 04/2012; 279(12):2120-33. · 4.25 Impact Factor
- The Journal of Rheumatology 06/2012; 39(6):1294-5. · 3.26 Impact Factor
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ABSTRACT: Igongsan (IGS), which is an herbal prescription composed of five different herbs, Ginseng Radix (root of Panax ginseng, Araliaceae), Atractylodis Rhizoma Alba (rhizome of Atractylodes Macrocephala, Compositae), Poria Sclerotium (sclerotium of Poria cocos, Polyporaceae), Glycyrrhizae Radix et Rhizoma (root and rhizome of Glycyrrhiza uralensis, Leguminosae), and Citri Unshius Pericarpium (Peel of Citrus unshiu, Rutaceae), has been traditionally used in Korea to treat a variety of inflammatory diseases. In this study, we investigated to elucidate the mechanism responsible for IGS's antiinflammatory effect in mouse peritoneal macrophages. The findings demonstrate that IGS inhibited the production of inflammatory cytokine and prostaglandins E2 . IGS inhibited the enhanced levels of cyclooxygenase-2 and inducible NO synthase caused by lipopolysaccharide (LPS). Additionally, it was shown that the antiinflammatory effect of IGS is through regulating the activation of nuclear factor-kappa B and caspase-1 in LPS-stimulated mouse peritoneal macrophages. These results provide novel insights into the pharmacological actions of IGS as a potential candidate for development of new drugs to treat inflammatory diseases. Discussion and conclusion: These results provide novel insights into the pharmacological actions of IGS as a potential candidate for development of new drugs to treat inflammatory diseases. Copyright © 2013 John Wiley & Sons, Ltd.Phytotherapy Research 08/2013; · 2.07 Impact Factor