Addition of interleukin 1 (IL1) and IL17 soluble receptors to a tumour necrosis factor alpha soluble receptor more effectively reduces the production of IL6 and macrophage inhibitory protein-3alpha and increases that of collagen in an in vitro model of rheumatoid synoviocyte activation

Chevrel, Guillaume

doi:10.1136/ard.61.8.730

Cited by 24 publications

(19 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Pathologically, this cytokine can activate and enhance all mechanisms of tissue injury that have been described previously in rheumatoid arthritis. In particular, IL-17 can up-regulate and/or synergize with local inflammatory mediators such as IL-6 [61,62], IL-1b and TNF-a [61][62][63], pro-oxidants such as nitric oxide [64], as well as promoting extracellular matrix injury through stimulation of production of matrix metalloproteinases (MMP) [65,66] and inhibition of matrix repair components such as proteoglycans and collagens [67,68]. Furthermore, bone injury is enhanced [69] through promotion of osteoclastogenesis via osteoclast activating factor [57].…”

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

Afzali

Lombardi

Lechler

et al. 2007

Clinical and Experimental Immunology

644

470

View full text Add to dashboard Cite

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

Afzali

Lombardi

Lechler

et al. 2007

Clinical and Experimental Immunology

644

470

View full text Add to dashboard Cite

“…In addition, this T cell cytokine has been shown to have additive or even synergistic effects with TNF and IL-1 on cytokine induction and tissue destruction (26)(27)(28)(29)(30). Of note, an IL-1-independent role for IL-17 in synovial inflammation and joint destruction in CIA has been reported (17), whereas the bone-erosive effect of IL-17 in vivo is strongly mediated by RANKL (31).…”

mentioning

confidence: 99%

Tumor necrosis factor–interleukin‐17 interplay induces S100A8, interleukin‐1β, and matrix metalloproteinases, and drives irreversible cartilage destruction in murine arthritis: Rationale for combination treatment during arthritis

Koenders¹,

Marijnissen²,

Devesa³

et al. 2011

Arthritis & Rheumatism

125

View full text Add to dashboard Cite

Objective. To examine whether synovial interleukin-17 (IL-17) expression promotes tumor necrosis factor (TNF)-induced joint pathologic processes in vivo, and to analyze the surplus ameliorative value of neutralizing IL-17 in addition to TNF during collageninduced arthritis (CIA).Methods. Adenoviral vectors were used to induce overexpression of IL-17 and/or TNF in murine knee joints. In addition, mice with CIA were treated, at different stages of arthritis, with soluble IL-17 receptor (sIL-17R), TNF binding protein (TNFBP), or the combination.Results. Overexpression of IL-17 and TNF resulted in joint inflammation and bone erosion in murine knees. Interestingly, IL-17 strikingly enhanced both the joint-inflammatory and joint-destructive capacity of TNF. Further analysis revealed a strongly enhanced up-regulation of S100A8, IL-1␤, and matrix metalloproteinase (MMP) messenger RNA, only when both TNF and IL-17 were present. Moreover, the increase in irreversible cartilage destruction was not merely the result of enhanced inflammation, but also was associated with a direct synergistic effect of these cytokines in the joint. S100A9 deficiency in mice protected against IL-17/TNF-induced expression of cartilage NITEGE neoepitopes. During established arthritis, the combination of sIL-17R and TNFBP was more effective than the anticytokine treatments alone, and significantly inhibited further joint inflammation and cartilage destruction.Conclusion. Local synovial IL-17 expression enhances the role of TNF in joint destruction. Synergy between TNF and IL-17 in vivo results in striking exaggeration of cartilage erosion, in parallel with a synergistic up-regulation of S100A8, IL-1␤, and erosive MMPs. Moreover, neutralizing IL-17 in addition to TNF further improves protection against joint damage and is still effective during late-stage CIA. Therefore, compared with anti-TNF alone, combination blocking of TNF and IL-17 may have additional therapeutic value for the treatment of destructive arthritis.Rheumatoid arthritis (RA) is a chronic disorder with unknown etiology. It is characterized by autoimmunity, infiltration of joint synovium by activated inflammatory cells, synovial hyperplasia, and progressive destruction of cartilage and bone. In the last decade, Supported by grants from the Dutch Arthritis Association (NR 00-1-302) and from the Stichting De Drie Lichten,

show abstract

“…However, therapies that focus on blocking TNF-␣ or IL-1 are not always effective, implicating that other cytokines might be interesting as additional targets. Simultaneous inhibition of several proinflammatory cytokines has shown promising results in vitro (1,2) and may be the best approach to increasing the percentage of responding patients as well as the responses of individual patients.…”

mentioning

confidence: 99%

Interleukin-17 Acts Independently of TNF-α under Arthritic Conditions

Koenders

Lubberts

Loo

et al. 2006

The Journal of Immunology

118

View full text Add to dashboard Cite

The proinflammatory T cell cytokine IL-17 is a potent inducer of other cytokines such as IL-1 and TNF-α. The contribution of TNF in IL-17-induced joint inflammation is unclear. In this work we demonstrate using TNF-α-deficient mice that TNF-α is required in IL-17-induced joint pathology under naive conditions in vivo. However, overexpression of IL-17 aggravated K/B×N serum transfer arthritis to a similar degree in TNF-α-deficient mice and their wild-type counterparts, indicating that the TNF dependency of IL-17-induced pathology is lost under arthritic conditions. Also, during the course of the streptococcal cell wall-induced arthritis model, IL-17 was able to enhance inflammation and cartilage damage in the absence of TNF. Additional blocking of IL-1 during IL-17-enhanced streptococcal cell wall-induced arthritis did not reduce joint pathology in TNF-deficient mice, indicating that IL-1 is not responsible for this loss of TNF dependency. These data provide further understanding of the cytokine interplay during inflammation and demonstrate that, despite a strong TNF dependency under naive conditions, IL-17 acts independently of TNF under arthritic conditions.

show abstract

Addition of interleukin 1 (IL1) and IL17 soluble receptors to a tumour necrosis factor alpha soluble receptor more effectively reduces the production of IL6 and macrophage inhibitory protein-3alpha and increases that of collagen in an in vitro model of rheumatoid synoviocyte activation

Cited by 24 publications

References 15 publications

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

Tumor necrosis factor–interleukin‐17 interplay induces S100A8, interleukin‐1β, and matrix metalloproteinases, and drives irreversible cartilage destruction in murine arthritis: Rationale for combination treatment during arthritis

Interleukin-17 Acts Independently of TNF-α under Arthritic Conditions

Contact Info

Product

Resources

About