The Role of T-lymphocytes and Cytokines in Rheumatoid Arthritis

Smolen, Josef S.; Tohidast‐Akrad, Makiyeh; Gal, Adrian Florin; Kunaver, M.; Eberl, Gérard; Zenz, Peter; Falus, András; Steiner, Günter

doi:10.3109/03009749609082660

Cited by 48 publications

(28 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During RA development, proinflammatory cytokines, such as TNF-␣, IL-1␤, INF-␥, and IL-2, play important roles in chronic joint inflammation and the acceleration of pannus formation and in the mediation of cartilage and bone destruction (Smolen et al, 1996;Lü nemann et al, 2002). Therefore, the regulations and/or normalizations of these cytokine levels are probably important from the therapeutic standpoint.…”

Section: Discussionmentioning

confidence: 99%

Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on the Reduction of Joint Inflammation in Experimental Rheumatoid Arthritis

Jin

Chae²,

Kim³

et al. 2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

This study focused on the potential therapeutic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on collagen-induced arthritis (CIA) and on the elucidation of the mechanisms involved. DBA/1J mice with established CIA were treated with various amount of recombinant soluble human TRAIL. The effects of TRAIL on the development and severity of CIA in this DBA/1J mouse model were assessed clinically and histologically, and a detailed investigation was conducted on proinflammatory cytokine and anticollagen-specific antibody levels. Cellular immunity was evaluated by investigating the proliferative responses and cytokine release profiles of splenocytes after TRAIL treatment. TRAIL treatment significantly reduced the severity and incidence of CIA, joint swelling, erythema, and edema. Histologic evaluations revealed that inflammatory cell infiltration, cartilage destruction, and bone erosion were significantly reduced in joints of TRAIL-treated mice with dose-dependent manner. TRAIL treatment also strongly decreased and/or normalized the productions of proinflammatory cytokines and of anti-collagen-specific antibodies in the sera of CIA mice. Furthermore, in vitro studies with primary splenocytes showed the cytotoxic effect of TRAIL on activated lymphocytes, with reduction of inflammatory cytokine release. These findings show that TRAIL administration is an effective anti-inflammatory treatment that prevents the development and progression of CIA in DBA/1J mice, and they suggest that TRAIL might be considered a potential treatment for human RA.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on the Reduction of Joint Inflammation in Experimental Rheumatoid Arthritis

Jin

Chae²,

Kim³

et al. 2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…The mechanism and pathogenesis of RA have not been fully clarified. RA has traditionally been assumed to be a Th1-type disease (28,29). However, recent studies revealed a new lineage of effector CD4 ϩ T cells characterized by the production of IL-17, and this Th17 lineage plays an essential role in both the development of autoimmune arthritis (30,31) and bone destruction (32).…”

mentioning

confidence: 99%

Hepatocyte Growth Factor Significantly Suppresses Collagen-Induced Arthritis in Mice

Okunishi

Dohi

Fujio

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Hepatocyte growth factor (HGF) plays an important role in angiogenesis, cell proliferation, antifibrosis, and antiapoptosis. Moreover, recent studies have highlighted the immunosuppressive effect of HGF in animal models of allogenic heart transplantation and autoimmune myocarditis and in studies in vitro as well. We also reported that HGF significantly suppresses dendritic cell function, thus down-regulating Ag-induced Th1-type and Th2-type immune responses in allergic airway inflammation. However, the immunosuppressive effect of HGF in many other situations has not been fully clarified. In the present study, using a mouse model of collagen-induced arthritis (CIA) and experiments in vitro, we examined the effect of HGF on autoimmune arthritis and then elucidated the mechanisms of action of HGF. To achieve sufficient delivery of HGF, we used biodegradable gelatin hydrogels as a carrier. HGF suppressed Ag-induced T cell priming by regulating the functions of dendritic cells in the Ag-sensitization phase with down-regulation of IL-10. In contrast, under continuous Ag stimulation HGF induced IL-10-producing immunocytes both in vivo and in vitro. Moreover, HGF potently inhibited the development of CIA with enhancing the Th2-type immune response. We also confirmed that HGF significantly suppressed the production of IL-17 by immunocytes. These results indicate that HGF suppresses the development of CIA through different ways at different phases. They also suggest that HGF could be an attractive tool for treating patients with rheumatoid arthritis.

show abstract

“…Transduction of NFκB leads to the activation of various genes including those for various pro-inflammatory cytokines and metalloproteinases. The NFκB activating TNF and IL-1 are both important factors in the pathogenesis of joint destruction associated with RA [37][38][39] and leflunomide appears to inhibit TNF and IL-1 mediated signal transduction.…”

Section: In Vitro Studies and Mechanism Of Actionmentioning

confidence: 98%

Leflunomide: a novel DMARD for the treatment of rheumatoid arthritis

Alldred

Emery

2001

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

Leflunomide (Arava(trade mark), Hoescht Marion Roussel, now Aventis Pharma) is a new, oral disease modifying antirheumatic drug (DMARD) for the treatment of active rheumatoid arthritis (RA). It is a novel isoxazole derivative, which has shown both anti-inflammatory and immunomodulatory properties. Leflunomide primarily acts by inhibiting the de novo synthesis of pyrimidine nucleotides (and consequently DNA and RNA) in immune response cells, particularly activated T-cells. It also inhibits tyrosine kinases, with a subsequent reduction in the pro-inflammatory cytokines, TNF and IL-1. Leflunomide is significantly more effective than placebo and equivalent to sulfasalazine and methotrexate in short-term (26 - 52 week) studies, as measured by American College of Rheumatology (ACR) criteria. It has shown significant improvements in functional disability and health related quality of life and has consistently been shown to slow radiographic progression of RA. Leflunomide has a rapid onset of action (within 4 weeks) which is significantly faster than placebo and sulfasalazine. Leflunomide was well-tolerated in clinical trials with no serious adverse effects occurring. The most common side effects were gastrointestinal disturbances, reversible alopecia, rash, hypertension and abnormal liver function tests. Most of these were mild to moderate and resolved without any complications. In summary leflunomide is an effective and well-tolerated DMARD that is a welcome addition to the currently available DMARDs for the treatment of this disabling condition.

show abstract

The Role of T-lymphocytes and Cytokines in Rheumatoid Arthritis

Cited by 48 publications

References 24 publications

Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on the Reduction of Joint Inflammation in Experimental Rheumatoid Arthritis

Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on the Reduction of Joint Inflammation in Experimental Rheumatoid Arthritis

Hepatocyte Growth Factor Significantly Suppresses Collagen-Induced Arthritis in Mice

Leflunomide: a novel DMARD for the treatment of rheumatoid arthritis

Contact Info

Product

Resources

About