Cytokine Pathways and Joint Inflammation in Rheumatoid Arthritis

Choy, Ernest; Panayi, G. S.

doi:10.1056/nejm200103223441207

Cited by 2,016 publications

(1,426 citation statements)

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“…Joint histopathology in this model is very similar to that seen in rheumatoid arthritis (RA), a disease typified by recurrent cycles of joint inflammation and gradual joint destruction. 21,22 In addition, a granulomatous inflammatory response, similar to that responsible for inactivating tuberculosis bacilli by walling off the invading bacteria, occurs in the liver and spleen of these animals at sites of SCW deposition. [18][19][20] …”

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confidence: 99%

Turmeric Extracts Containing Curcuminoids Prevent Experimental Rheumatoid Arthritis

et al. 2006

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Turmeric has been used for centuries in Ayurvedic medicine as a treatment for inflammatory disorders including arthritis. On the basis of this traditional usage, dietary supplements containing turmeric rhizome and turmeric extracts are also being used in the western world for arthritis treatment and prevention. However, to our knowledge, no data are available regarding antiarthritic efficacy of complex turmeric extracts similar in composition to those available for use as dietary supplements. Therefore, the studies described here were undertaken to determine the in vivo efficacy of well-characterized curcuminoid-containing turmeric extracts in the prevention or treatment of arthritis using streptococcal cell wall (SCW)-induced arthritis, a well-described animal model of rheumatoid arthritis (RA). Arthritic index, a clinical measure of joint swelling, was used as the primary endpoint for assessing the effect of extracts on joint inflammation. An essential oil-depleted turmeric fraction containing 41% of the three major curcuminoids was efficacious in preventing joint inflammation when treatment was started before, but not after, the onset of joint inflammation. A commercial sample containing 94% of the three major curcuminoids was more potent in preventing arthritis than the essential oil-depleted turmeric fraction when compared by total curcuminoid dose per body weight. In conclusion, these data (1) document the in vivo antiarthritic efficacy of an essential oil-depleted turmeric fraction and (2) suggest that the three major curcuminoids are responsible for this antiarthritic effect, while the remaining compounds in the crude turmeric extract may inhibit this protective effect.

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Turmeric Extracts Containing Curcuminoids Prevent Experimental Rheumatoid Arthritis

et al. 2006

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“…These proinflammatory mediators, in turn, cause chronic inflammation and joint destruction (10). Studies in both experimental animal models and patients suggest that the cytokine interleukin-1 (IL-1) plays an important role in promoting tissue inflammation and remodeling (11)(12)(13)(14).…”

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Anakinra, a recombinant human interleukin‐1 receptor antagonist (r‐metHuIL‐1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo‐controlled trial

Fleischmann¹,

Schechtman²,

Bennett

et al. 2003

Arthritis & Rheumatism

356

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for the 990757 Study GroupObjective. To evaluate the safety of anakinra (a recombinant human interleukin-1 receptor antagonist) in a large population of patients with rheumatoid arthritis (RA), typical of those seen in clinical practice.Methods. A total of 1,414 patients were randomly assigned to treatment with 100 mg of anakinra or placebo, administered daily by subcutaneous injection. Background medications included disease-modifying antirheumatic drugs, corticosteroids, and nonsteroidal antiinflammatory drugs, alone or in combination. The primary end point was safety, which was evaluated by adverse events (including infections), discontinuation from study due to adverse events, and death.Results. Safety was evaluated in 1,399 patients (1,116 in the anakinra group and 283 in the placebo group; 15 patients were randomized but did not receive any study drug) during the initial 6-month, doubleblind, placebo-controlled phase of this long-term safety study. Baseline demographics, disease characteristics, and concomitant medications were similar between the 2 groups. The study group included patients with numerous comorbid conditions and a wide range of RA disease activity. Serious adverse events occurred at a similar rate in the anakinra group and the placebo group (7.7% and 7.8%, respectively). Serious infectious episodes were observed more frequently in the anakinra group (2.1% versus 0.4% in the placebo group). The rate of withdrawal due to adverse events was 13.4% in the anakinra group and 9.2% in the placebo group.Conclusion. Results from this large, placebocontrolled safety study demonstrate that anakinra is safe and well tolerated in a diverse population of patients with RA, including those with comorbid conditions and those using multiple combinations of concomitant therapies. Although the frequency of serious infection was slightly higher in the anakinra group, no infection was attributed to opportunistic microorganisms or resulted in death.

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“…IL-1␤ occupies a prominent place in the hierarchy of proinflammatory cytokines associated with inflammatory, immune, and arthritic diseases (48). Among the plethora of genes under IL-1␤ control, cox-2 is particularly sensitive.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase 2–derived prostaglandin E₂ production by corticotropin‐releasing hormone contributes to the activated cAMP response element binding protein content in rheumatoid arthritis synovial tissue

McEvoy¹,

Bresnihan²,

FitzGerald³

et al. 2004

Arthritis & Rheumatism

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Objective. To determine a mechanism by which corticotropin-releasing hormone (CRH) promotes human inflammatory joint disease progression.Methods. An ex vivo synovial tissue culture system was established to investigate the functional properties of CRH at peripheral sites of inflammation. CRHand interleukin-1␤ (IL-1␤)-induced prostaglandin E 2 (PGE 2 ) production from 10 fresh rheumatoid arthritis (RA) synovial tissue (ST) explants was quantified using a competitive enzyme-linked immunosorbent assay. Modulation of PGE 2 levels was further examined following selective and nonselective cyclooxygenase 2 (COX-2) inhibition. Nuclear extracts were analyzed by electrophoretic mobility shift assays to determine functional cAMP response element binding protein (CREB) activity in response to CRH and PGE 2 in isolated primary synovial cell populations. Western blot analysis measured levels of total and activated (phosphospecific) CREB/activating transcription factor (ATF) family members prior to and following stimulation.Results. CRH, in a time-and dose-dependent manner, significantly (P ‫؍‬ 0.022) up-regulated PGE 2 production from 10 fresh RA ST explants. Costimulation of RA ST with CRH and IL-1␤ significantly augmented (P ‫؍‬ 0.036) the effects on PGE 2 production additively over 24 hours. We demonstrated that selective COX-2 inhibitors prevent the induction of PGE 2 by both CRH and IL-1␤. Further, we provided evidence that CRH and PGE 2 signal through the induction of CREB and phosphorylated CREB/ATF family members in RA ST and in isolated primary RA cell populations.Conclusion. Our findings underscore the pathogenic role that CRH may play in modulating inflammatory joint disease and establish the CREB/ATF family of transcription factors as principal effector molecules of proinflammatory mediator action in RA.

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Cytokine Pathways and Joint Inflammation in Rheumatoid Arthritis

Cited by 2,016 publications

References 65 publications

Turmeric Extracts Containing Curcuminoids Prevent Experimental Rheumatoid Arthritis

Turmeric Extracts Containing Curcuminoids Prevent Experimental Rheumatoid Arthritis

Anakinra, a recombinant human interleukin‐1 receptor antagonist (r‐metHuIL‐1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo‐controlled trial

Cyclooxygenase 2–derived prostaglandin E₂ production by corticotropin‐releasing hormone contributes to the activated cAMP response element binding protein content in rheumatoid arthritis synovial tissue

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Cytokine Pathways and Joint Inflammation in Rheumatoid Arthritis

Cited by 2,016 publications

References 65 publications

Turmeric Extracts Containing Curcuminoids Prevent Experimental Rheumatoid Arthritis

Turmeric Extracts Containing Curcuminoids Prevent Experimental Rheumatoid Arthritis

Anakinra, a recombinant human interleukin‐1 receptor antagonist (r‐metHuIL‐1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo‐controlled trial

Cyclooxygenase 2–derived prostaglandin E2 production by corticotropin‐releasing hormone contributes to the activated cAMP response element binding protein content in rheumatoid arthritis synovial tissue

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Cyclooxygenase 2–derived prostaglandin E₂ production by corticotropin‐releasing hormone contributes to the activated cAMP response element binding protein content in rheumatoid arthritis synovial tissue