Inhibition of IL6 in rheumatoid arthritis and juvenile idiopathic arthritis

The University of California, San Diego, CA, USA.
Experimental Cell Research (Impact Factor: 3.25). 03/2011; 317(9):1286-92. DOI: 10.1016/j.yexcr.2011.02.017
Source: PubMed


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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    • "Macrophage activation has been determined to perform an important role in the inflammatory process (Adamson and Leitinger, 2011; Beutler, 2000) and to generate potent pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, which induce inflammation and recruit other immune cells (Bunikowski et al., 2001). Although TNF-α and IL-6 are beneficial to host defenses , they can also trigger pathological conditions when expressed in excess quantities (Mircic and Kavanaugh, 2011). Additionally, higher levels of inflammatory cytokines have also been implicated in a variety of chronic inflammatory diseases including rheumatoid arthritis, psoriasis, and Crohn's disease (Guerreiro et al., 2009; Moudgil and Choubey, 2011). "
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    Molecular Medicine Reports 09/2011; 5(1):177-83. DOI:10.3892/mmr.2011.595 · 1.55 Impact Factor
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    ABSTRACT: High levels of cytokines in juvenile idiopathic arthritis (JIA) can alter target cell sensitivity to growth hormone (GH) leading to short stature in adulthood. We hypothesized that the down-regulation of GH receptor (GHR) gene expression could be involved in growth failure of children with JIA. In 18 (12 F and 6 M) prepubertal JIA patients and 13 age- and sex-matched healthy children, we evaluated serum growth-promoting factors and inflammatory indexes. We also measured GHR gene expression, by real-time PCR, in lymphocytes of patients and controls. All parameters were evaluated in patients before and after treatment of JIA. The most interesting (p = 0.007) result was the increase in GHR mRNA expression in all JIA patients. Moreover, we observed a significant (p = 0.0156) decrease in IL-6 levels in JIA patients after 2 years of therapy (19.37 ± 41.01) with respect to basal values (90.84 ± 124.71). On the contrary, IGF-I significantly (p = 0.0005) increased to a mean SDS value of 0 (range -1.69 to +1.70 SDS) with respect to values at disease onset (-0.64 SDS). Our preliminary data suggest that the restoration of both GHR gene expression and IGF-I secretion correlate with inactive disease in JIA children.
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