Interleukin‐1‐induced interleukin‐6 is required for the inhibition of proteoglycan synthesis by interleukin‐1 in human articular cartilage

Nietfeld, J. J.; Wilbrink, B.; Helle, M.; Roy, J. L. A. M. Van; Otter, W. Den; Swaak, A. J. G.; Huber-Bruning, O.

doi:10.1002/art.1780331113

Cited by 119 publications

(62 citation statements)

References 22 publications

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“…In fact, IL-1␤, together with TNF␣, induces the release of tissue-damaging enzymes from synovial cells and articular chondrocytes and activates osteoclasts (30,31). IL-6 participates together with IL-1 in the catabolism of connective tissue components at inflammation sites (32,33), and activates osteoclasts, resulting in joint destruction (34). It is likely that a decrease in IL-6 and IL-1␤ is one of the factors involved in the amelioration of articular lesions upon anti-IL-18 treatment in our experimental model.…”

Section: Discussionmentioning

confidence: 92%

Role of interleukin‐18 in experimental group B streptococcal arthritis

Tissi¹,

McRae²,

Ghayur³

et al. 2004

Arthritis & Rheumatism

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Objective. To assess the role of interleukin-18 (IL-18) in the evolution of septic arthritis induced by group B streptococci (GBS) in mice.Methods. CD1 mice were inoculated intravenously with 8 ؋ 10 6 colony-forming units (CFU) of type IV GBS (strain 1/82), and administered intraperitoneally 1 hour before infection with anti-IL-18 monoclonal antibodies (0.25 mg/mouse). In a subsequent set of experiments, mice infected with a suboptimal arthritogenic dose of GBS (4 ؋ 10 6 CFU/mouse) were administered different doses of recombinant IL-18 for 4 days, starting 1 hour after infection. Mortality, evolution of arthritis, bacterial clearance, joint histopathology, and cytokine production were examined in infected mice that did or did not receive treatment with anti-IL-18 antibodies or IL-18.Results. IL-18 was produced during GBS infection. Neutralization of IL-18 resulted in a decrease in mortality rates, and in the incidence and severity of arthritis. Amelioration of arthritis was accompanied by a dramatic reduction in local IL-1␤, IL-6, macrophage inflammatory protein 1␣ (MIP-1␣) and MIP-2 production, and reduced bacterial burden. Administration of exogenous IL-18 resulted in increased mortality rates and increased incidence and severity of GBS arthritis, concomitant with a higher number of GBS and increased levels of IL-6, IL-1␤, MIP-1␤, and MIP-2 production in the joints.Conclusion. The present study indicated some involvement of IL-18 in the pathogenesis of GBSinduced arthritis. The role of IL-18 in joint pathology is shown by a regulatory effect on inflammatory mediator levels and local cell influx. Thus, IL-18 should be regarded as a potential therapeutic target in GBS infection and arthritis.

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Section: Discussionmentioning

confidence: 92%

Role of interleukin‐18 in experimental group B streptococcal arthritis

Tissi¹,

McRae²,

Ghayur³

et al. 2004

Arthritis & Rheumatism

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“…It is reported to be produced constitutively by both synoviocytes (22) and chondrocytes (23), as well as by T cells and B cells (24). Its production by synoviocytes and chondrocytes is markedly up-regulated by cytokines, such as IL-1 and TNF (22,23,25), and by transforming growth factor P (TGFP) (23). IL-6 synthesis by peripheral blood mononuclear cells can also be induced by TNFa (26) and TGFP (27).…”

Section: Discussionmentioning

confidence: 99%

“…IL-6 synthesis by peripheral blood mononuclear cells can also be induced by TNFa (26) and TGFP (27). Production of IL-6 by the higher proportion of activated mononuclear cells in the rheumatoid joint may partly account for the generally higher levels of IL-6 found in the synovial fluid of patients with rheumatoid arthritis (RA) compared with those with osteoarthritis (22,25,28,29).…”

Section: Discussionmentioning

confidence: 99%

Elevated synovial fluid levels of interleukin‐6 and tumor necrosis factor associated with early experimental canine osteoarthritis

Venn

Nietfeld

Duits

et al. 1993

Arthritis & Rheumatism

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Objective. To measure levels of cytokines, proteases, and glycosaminoglycans (GAG) in synovial fluid (SF) From the knees of animals with experimental osteoarthritis (OA) and from their contralateral (control) knees, and to compare and correlate these values with each other as well as with measures of proteoglycan synthesis in the corresponding articular cartilage. This study will help to identify cytokines of potential importance in the early stages of the development of OA.Methods. OA was induced in 12 mature animals by sectioning the anterior cruciate ligament. After 3 months, SF From the operated and contralateral (control) knee joints was assayed for interleukind (IL-6), tumor necrosis Factor (TNF), IL-1, latent metalloproteinase, and sulfated GAG. Proteoglycan synthesis in the corresponding articular cartilage was also measured.Results. IL-6 levels in SF from the operated joint compared with the control joint were significantly ele- Submitted for publication July 9, 1992; accepted in revised form January 6, 1993. vated in 11 of 12 animals. TNF levels were also elevated in 10 of 11 SF samples from operated joints, but to a lesser extent than those of IL-6. IL-1 and IL-1 inhibitors were undetectable in either the operated or control joint SF. The GAG concentration was elevated in SF from experimental OA joints. This elevation correlated with that of TNF, but not IL-6. There was no significant difference in the concentration of APMA-activatable metalloproteinase. The rate of proteoglycan synthesis was higher in the cartilage from the operated joint in 8 of 12 animals, and the mean rate of synthesis was significantly higher than in the control joint. There was a positive correlation between this increase in cartilage proteoglycan synthesis (operated versus control) and the increase in SF IL-6, but there was no correlation with the levels of TNF or GAG.Conclusion. This is the first study of SF levels of cytokines in early experimental OA. Our results show surprisingly high levels of IL-6 in operated joints, where the cytokine could act directly on the chondrocytes, and thus play a role in mediating their responses to cartilage injury.

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“…IL-6 is in its effects similar to IL-1, but shows an overall weaker potential to inhibit proteoglycan synthesis (Guerne et al, 1999). It is needed for prolonged proteoglycan suppression by IL-1 (Nietfeld et al, 1990) and enhances MMP and aggrecanase expression and activity in articular cartilage (Flannery et al, 2000;Kusano et al, 1998). LIF, a protein belonging to a family of IL-6 related proteins, is also a suppressor of proteoglycan expression in articular chondrocytes and is able to increase MMP-13 production (Bell et al, 1995;Varghese et al, 1999).…”

Section: Interleukin-1 Down-regulates Anabolic and Upregulates Catabomentioning

confidence: 99%

IL-1ß and BMPs - Interactive players of cartilage matrix degradation and regeneration

Aigner

Söeder²,

Haag³

2006

eCM

100

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Intact human adult articular cartilage is central for the functioning of the articulating joints. This largely depends on the integrity of its extracellular matrix, given the high loading forces during movements in particular in the weight-bearing joints. Unlike the first impression of a more or less static tissue, articular cartilage shows -albeit in the adult organism -a slow tissue turnover. Thus, one of the most important questions in osteoarthritis research is to understand the balance of catabolic and anabolic factors in articular cartilage as this is the key to understand the biology of cartilage maintenance and degeneration.Anabolic and catabolic pathways are very much intermingled in articular cartilage. The balance between anabolism and catabolism is titrated on numerous levels, starting from the mediator-synthesizing cells which express either catabolic or anabolic factors. Also, on the level of the effector cells (i.e. chondrocytes) anabolic and catabolic gene expression compete for a balance of matrix homeostasis, namely the synthesis of matrix components and the expression and activation of matrix-degrading proteases. Also, there are multiple layers of intracellular cross-talks in between the anabolic and catabolic signalling pathways. Maybe the most important lesson from this overview is the notion that the anabolic-catabolic balance as such counts and not so much sufficient net anabolism or limited catabolism alone. Thus, it might be neither the aim of osteoarthritis therapy to foster anabolism nor to knock down catabolism, but the balance of anabolic-catabolic activities as a total needs proper titration and balancing.

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Interleukin‐1‐induced interleukin‐6 is required for the inhibition of proteoglycan synthesis by interleukin‐1 in human articular cartilage

Cited by 119 publications

References 22 publications

Role of interleukin‐18 in experimental group B streptococcal arthritis

Role of interleukin‐18 in experimental group B streptococcal arthritis

Elevated synovial fluid levels of interleukin‐6 and tumor necrosis factor associated with early experimental canine osteoarthritis

IL-1ß and BMPs - Interactive players of cartilage matrix degradation and regeneration

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