Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin‐17 receptor IgG1 Fc fusion protein

Bush, K. A.; Farmer, K.; Walker, Judith S.; Kirkham, Bruce

doi:10.1002/art.10173

Cited by 231 publications

(145 citation statements)

References 15 publications

(23 reference statements)

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“…However, during the later stage of the arthritis, T cell cytokines may be overruled by mediators produced by activated macrophages. It has been shown that IL-17 plays an inflammatory role in the initial phase of experimental arthritis (17,18). The present study makes it clear that after the first clinical signs of arthritis, neutralizing endogenous IL-17 is still of therapeutic value.…”

Section: Discussionmentioning

confidence: 52%

“…A single injection with anti-IL-17 antibody seems to be much more efficient than treatment with the soluble IL-17 receptor (sIL-17R):Fc fusion protein, as previously described (17,18). Since the treatment protocols are not identical between our previous study and the present study, we also treated CIA mice with the sIL-17R:Fc fusion protein starting after the onset of CIA (4 injections on alternative days using the same dose as described in ref.…”

Section: Discussionmentioning

confidence: 99%

“…IL-17 can stimulate the production of IL-1␤ and TNF␣ from macrophages (4) and triggers human synoviocytes to produce IL-6, IL-8, granulocytemacrophage colony-stimulating factor, and prostaglandin E 2 (2,16), suggesting that IL-17 could be an upstream mediator in the pathogenesis of arthritis. Early neutralization of endogenous IL-17 prior to the development of arthritis in the experimental arthritis model suppresses the onset of disease (17,18). Furthermore, IL-17 may be involved in tissue destruction.…”

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confidence: 99%

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Treatment with a neutralizing anti‐murine interleukin‐17 antibody after the onset of collagen‐induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

Lubberts¹,

Koenders²,

Oppers‐Walgreen³

et al. 2004

Arthritis & Rheumatism

659

457

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Objective. Interleukin-17 (IL-17) is a proinflammatory cytokine that is expressed in the synovium of rheumatoid arthritis (RA) patients. This T cell cytokine is implicated in the initiation phase of arthritis. However, the role of IL-17 during the effector phase of arthritis has still not been identified; this was the objective of the present study.Methods. Mice with collagen-induced arthritis (CIA) were treated with polyclonal rabbit anti-murine IL-17 (anti-IL-17) antibody-positive serum or normal rabbit serum after the first signs of arthritis. In addition, during a later stage of CIA mice were selected and treated with anti-IL-17 antibody or control serum. Arthritis was monitored visually, and joint pathology was examined radiologically and histologically. Systemic IL-6 levels were measured by enzyme-linked immunosorbent assay, and local synovial IL-1 and receptor activator of NF-B ligand (RANKL) expression was analyzed using specific immunohistochemistry.Results

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Treatment with a neutralizing anti‐murine interleukin‐17 antibody after the onset of collagen‐induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

Lubberts¹,

Koenders²,

Oppers‐Walgreen³

et al. 2004

Arthritis & Rheumatism

659

457

View full text Add to dashboard Cite

show abstract

“…Previous anti-IL-17 treatment during rat adjuvant arthritis has also shown significant suppression of radiological scores. 36 These findings suggest a possible beneficial effect of anti-IL-17 treatment in RA patients in the prevention of further bone damage during arthritic flares. The protective effect of neutralizing endogenous IL-17 reported here was supported by reduced synovial RANKL and cathepsin K expression.…”

Section: Discussionmentioning

confidence: 88%

Blocking of Interleukin-17 during Reactivation of Experimental Arthritis Prevents Joint Inflammation and Bone Erosion by Decreasing RANKL and Interleukin-1

Koenders

Lubberts

Oppers‐Walgreen

et al. 2005

The American Journal of Pathology

281

175

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Rheumatoid arthritis is characterized by an intermittent course of disease with alternate periods of remission and relapse. T cells, and in particular the T-cell cytokine interleukin-17 (IL-17), are expected to be involved in arthritic flares. Here, we report that neutralizing endogenous IL-17 during reactivation of antigen-induced arthritis prevents joint inflammation and bone erosion. Synovial IL-17 mRNA expression was clearly up-regulated during primary arthritis and was further enhanced after antigen rechallenge. Neutralization of IL-17 significantly prevented joint swelling at day 1 of flare and significantly suppressed joint inflammation and cartilage proteoglycan depletion at day 4, as assessed by histology. Blocking IL-17 also clearly reduced bone erosions. Cathepsin K, a marker of osteoclast-like activity, and synovial RANKL mRNA expression were both suppressed. The degree of bone erosions strongly correlated with the severity of joint inflammation, suggesting that anti-IL-17 treatment reduced bone erosion by suppressing joint inflammation. Interestingly, blocking IL-17 suppressed synovial expression of both IL-1␤ and tumor necrosis factor-␣, whereas blocking IL-1 did not affect tumor necrosis factor-␣ levels. These data indicate that IL-17 is an important upstream mediator in joint pathology Rheumatoid arthritis (RA) is a systemic joint disease characterized by progressive destructive joint inflammation. Although RA is considered an autoimmune disease, the autoantigen(s) is still not identified. Interestingly, CTLA4Ig treatment in patients with RA showed promising improvement of the ACR50 and ACR70 responses. 1 This treatment blocks the interaction of CD80/86 on antigen-presenting cells with CD28 on naïve T cells. This interaction is required for optimal T-cell activation. This study supports the theory that (CD4 ϩ ) T cells play a key role in the pathogenesis of RA. [2][3][4] The contribution of T cells in the joints can be related to antigen-dependent and -independent mechanisms, such as direct cell contact, which can induce cytokine and protease production by macrophages and fibroblasts. 5 Furthermore, RA is characterized by an intermittent course of the disease with alternate periods of remission and relapse. The cause of a flare-up reaction during RA is unclear, and both antigen-specific and antigen-nonspecific T cells may play a role. 4 Studies in animal models for experimental arthritis have resulted in better understanding of the role of different cell types and various cytokines during arthritic flares. In antigen-induced arthritis, the capacity to develop arthritis can be transferred by lymphocytes, 6 in particular by cell fractions enriched for T cells, and high

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“…As inflammation progresses in the joint, increased levels of IL-4, IL-6, monocyte chemotactic protein 1 (MCP-1)/CCL2, and TGF␤ can be detected (34). TNF␣, IL-1␤, IL-21, and IL-17 are all involved in the pathology of this disease, because their blockade ameliorates disease (35)(36)(37). AIA is not joint-specific but is associated with granuloma formation in various organs and tissues, such as the spleen, liver, bone marrow, skin, and eyes (38).…”

Section: Evaluation Of Therapeutic Targets In Animal Models Of Arthritismentioning

confidence: 99%

Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

Bevaart¹,

Vervoordeldonk²,

Tak³

2010

Arthritis & Rheumatism

232

193

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There are accumulating data describing the association between diabetes and cancer mortality from Westernised populations. There are no data describing the relationship between diabetes and cancer mortality in African or South Asian populations from developing countries. We explored the relationship of abnormal glucose tolerance and diabetes on cancer mortality risk in a large, multi‐ethnic cohort from the developing nation of Mauritius. Population‐based surveys were undertaken in 1987, 1992 and 1998. The 9559 participants comprised 66% of South Asian (Indian), 27% of African (Creole), and 7% of Chinese descent. Cox's proportional hazards model with time varying covariates was used to obtain hazard ratios (HRs) and 95% confidence intervals (95% CI) for risk of cancer mortality, after adjustment for confounding factors. In men, but not women, cancer mortality risk increased with rising 2h‐PG levels with HR for the top versus bottom quintile of 2.77 (95%CI: 1.28 to 5.98). South Asian men with known diabetes had a significantly greater risk of cancer mortality than those with normal glucose tolerance (NGT) HR: 2.74 (95%CI: 1.00‐7.56). Overall, impaired glucose tolerance was associated with an elevated risk of cancer mortality compared to NGT (HR: 1.47, 95% CI: 0.98–2.19), though this was not significant. We have shown that the association between abnormal glucose tolerance and cancer extends to those of African and South Asian descent. These results highlight the importance of understanding this relationship in a global context to direct future health policy given the rapid increase in type 2 diabetes, especially in developing nations.

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Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin‐17 receptor IgG1 Fc fusion protein

Cited by 231 publications

References 15 publications

Treatment with a neutralizing anti‐murine interleukin‐17 antibody after the onset of collagen‐induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

Treatment with a neutralizing anti‐murine interleukin‐17 antibody after the onset of collagen‐induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

Blocking of Interleukin-17 during Reactivation of Experimental Arthritis Prevents Joint Inflammation and Bone Erosion by Decreasing RANKL and Interleukin-1

Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

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