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

Lubberts, Erik; Koenders, Marije I.; Oppers‐Walgreen, Birgitte; Bersselaar, Liduine van den; Roo, Christina J. J. Coenen-de; Joosten, Leo A. B.; Berg, Wim B. van den

doi:10.1002/art.20001

Cited by 659 publications

(507 citation statements)

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“…It offers great hope for potential treatment of diseases where IL-17 is recognized as the key inducer of inflammation, as is now Highlights 2871 well documented in arthritis [29], asthma [30], inflammatory bowel disease [31,32] and intra-abdominal abscesses [33]. In multiple sclerosis, little is known about the actual importance of IL-17, although increased numbers of IL-17 mRNA-expressing cells were found to correlate with disease exacerbation [34].…”

Section: Discussionmentioning

confidence: 99%

Development of an anti‐IL‐17A auto‐vaccine that prevents experimental auto‐immune encephalomyelitis

2006

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IL-17 has been associated with multiple inflammatory disorders such as rheumatoid arthritis, asthma and multiple sclerosis. As these diseases require long-term treatment we turned to an auto-vaccine strategy for IL-17 neutralization in vivo. Mouse IL-17A was covalently linked to ovalbumin and used to immunize C57BL/6 mice. This vaccine induced the production of antibodies that blocked IL-17A bioactivity in vitro but did not react with the other IL-17 isoforms, including IL-17F. As the half-life of the Ab titers after the last immunogen administration was approximately 4 months, the vaccine provides for long lasting and selective inhibition of IL-17A activity in vivo. A monoclonal Ab (mAb) derived from these mice showed the same specificity for IL-17A. To test the ability of the vaccine to confer protection against an IL-17-dependent disorder, SJL mice were vaccinated with IL-17-OVA and encephalomyelitis (EAE) was induced by proteolipid protein (PLP) peptide 139-151. Vaccinated mice were completely protected against the disease. The above-mentioned anti-IL-17A mAb also prevented EAE development. The absence of clinical symptoms contrasted with unaltered PLP-induced cytokine production in vitro and unmodified anti-PLP IgG titers and isotypes. These results suggest that an anti-IL-17A auto-vaccine offers new perspectives for therapy of autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Development of an anti‐IL‐17A auto‐vaccine that prevents experimental auto‐immune encephalomyelitis

2006

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“…We obtained [5,6,8,11,12,14,15(N)-3 H]-prostaglandin E 2 (PGE 2 ) from Amersham Biosciences (Barcelona, Spain). Cyclooxygenase 2 (COX-2)-specific polyclonal antibody was purchased from Cayman Chemical (Ann Arbor, MI).…”

Section: Methodsmentioning

confidence: 99%

“…This model of rheumatoid arthritis exhibits clinical and histopathologic features similar to those of the human disease (3). Studies of CIA models have helped in our understanding of the molecular mechanisms involved in the pathogenesis of chronic inflammatory joint disease, and the CIA model has been widely used in the search for new antiarthritis treatments (4)(5)(6).…”

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confidence: 99%

Influence of heme oxygenase 1 modulation on the progression of murine collagen‐induced arthritis

Devesa¹,

Ferrándiz²,

Terencio³

et al. 2005

Arthritis & Rheumatism

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Objective. Heme oxygenase 1 (HO-1) can be induced by inflammatory mediators as an adaptive response. The objective of the present study was to determine the consequences of HO-1 modulation in the murine collagen-induced arthritis (CIA) model.Methods. DBA/1J mice were treated with an inhibitor of HO-1, tin protoporphyrin IX (SnPP), or with an inducer of HO-1, cobalt protoporphyrin IX (CoPP), from day 22 to day 29 after CIA induction. The clinical evolution of disease was monitored visually. At the end of the experiment, joints were examined for histopathologic changes. Cytokine levels in paws were measured by enzyme-linked immunosorbent assay. Levels of HO-1, cyclooxygenase 2 (COX-2), and prostaglandin E 2 (PGE 2 ) were determined. Effects of treatments on the early phase of disease and after prophylactic administration were also assessed.Results. CoPP strongly induced HO-1, resulting in the inhibition of cartilage erosion accompanied by extensive fibrosis in the joint. Levels of tumor necrosis factor ␣ (TNF␣), interleukin-2 (IL-2), and IL-10 were inhibited by CoPP, whereas levels of vascular endothelial growth factor were increased. Treatment with SnPP significantly reduced the severity of CIA, with inhibition of joint inflammation and cartilage destruction. The levels of PGE 2 , IL-1␤, and TNF␣ were also significantly reduced by SnPP treatment, which did not modify COX-2 protein expression. SnPP was more effective than CoPP in preventing the development of CIA (prophylactic administration).Conclusion. HO-1 is induced during CIA. Although overexpression of this protein causes some beneficial effects, strategies aimed at HO-1 overexpression cannot slow the progression of the chronic inflammatory disease, whereas treatment with SnPP, which inhibits HO-1, exerts prophylactic and therapeutic effects.

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“…Despite the similarity of Th1 and Th17, the efficacy of anti-IL-17 mAb treatment in GPI-induced arthritis was more marked than in CIA. In the CIA model, administration of anti-IL-17 antibodies during the induction phase of arthritis was shown to only partially inhibit the development of arthritis (21). This difference between GPIinduced arthritis and CIA may reflect a more substantial contribution from cells of the Th17 lineage.…”

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confidence: 97%

Crucial role of the interleukin‐6/interleukin‐17 cytokine axis in the induction of arthritis by glucose‐6‐phosphate isomerase

Iwanami¹,

Matsumoto²,

Tanaka-Watanabe³

et al. 2008

Arthritis & Rheumatism

124

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Objective. To clarify the glucose-6-phosphate isomerase (GPI)-specific CD4؉ T cell lineage involved in GPI-induced arthritis and to investigate their pathologic and regulatory roles in the induction of the disease.Methods. DBA/1 mice were immunized with GPI to induce arthritis. CD4؉ T cells and antigen-presenting cells were cocultured with GPI, and cytokines in the supernatant were analyzed by enzyme-linked immunosorbent assay. Anti-interferon-␥ (anti-IFN␥) monoclonal antibody (mAb), anti-interleukin-17 (anti-IL-17) mAb, or the murine IL-6 receptor (IL-6R) mAb MR16-1 was injected at different time points, and arthritis development was monitored visually. After MR16-1 was injected, percentages of Th1, Th2, Th17, and Treg cells were analyzed by flow cytometry, and CD4؉ T cell proliferation was analyzed using carboxyfluorescein diacetate succinimidyl ester.Results. GPI-specific CD4؉ T cells were found to be differentiated to Th1 and Th17 cells, but not Th2 cells. Administration of anti-IL-17 mAb on day 7 significantly ameliorated arthritis (P < 0.01), whereas administration of anti-IFN␥ mAb exacerbated arthritis.Neither anti-IL-17 mAb nor anti-IFN␥ mAb administration on day 14 ameliorated arthritis. Administration of MR16-1 on day 0 or day 3 protected against arthritis induction, and MR16-1 administration on day 8 significantly ameliorated existing arthritis (P < 0.05). After administration of MR16-1, there was marked suppression of Th17 differentiation, without an increase in Th1, Th2, or Treg cells, and CD4؉ T cell proliferation was also suppressed.Conclusion. IL-6 and Th17 play an essential role in GPI-induced arthritis. Since it has previously been shown that treatment with a humanized anti-IL-6R mAb has excellent effects in patients with rheumatoid arthritis (RA), we propose that the IL-6/IL-17 axis might also be involved in the generation of RA, especially in the early effector phase.

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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

Cited by 659 publications

References 40 publications

Development of an anti‐IL‐17A auto‐vaccine that prevents experimental auto‐immune encephalomyelitis

Development of an anti‐IL‐17A auto‐vaccine that prevents experimental auto‐immune encephalomyelitis

Influence of heme oxygenase 1 modulation on the progression of murine collagen‐induced arthritis

Crucial role of the interleukin‐6/interleukin‐17 cytokine axis in the induction of arthritis by glucose‐6‐phosphate isomerase

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