A single intra‐articular injection with <scp>IL</scp>‐4 plus <scp>IL</scp>‐10 ameliorates blood‐induced cartilage degeneration in haemophilic mice

Meegeren, M.E.R. van; Roosendaal, G.; Coeleveld, K.; Nieuwenhuizen, Laurens; Mastbergen, S.C.; Lafeber, Floris P. J. G.

doi:10.1111/bjh.12148

Cited by 37 publications

(41 citation statements)

References 33 publications

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“…Both IL-4 and IL-10 are potent anti-inflammatory mediators that individually and synergistically reduce the production of IL-1β and TNF-α. 41,42 The results of the present study, in the context of previous clinical and basic science findings, support a transition away from LR-PRP and toward LP-PRP in the clinical context for intra-articular use; LPPRP activates fewer proinflammatory cytokines and more anti-inflammatory cytokines while still delivering an increased concentration of platelets to the site of injury.…”

Section: Discussionsupporting

confidence: 84%

The Effect of Platelet-Rich Plasma Formulations and Blood Products on Human Synoviocytes

et al. 2014

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Background The effect of platelet-rich plasma (PRP) on chondrocytes has been studied in cell and tissue culture, but considerably less attention has been given to the effect of PRP on synoviocytes. Fibroblast-like synoviocytes (FLS) compose 80% of the normal human synovium and produce cytokines and matrix metalloproteinases that can mediate cartilage catabolism. Purpose To compare the effects of leukocyte-rich PRP (LR-PRP), leukocyte-poor PRP (LP-PRP), red blood cell (RBC) concentrate, and platelet-poor plasma (PPP) on human FLS to determine whether leukocyte and erythrocyte concentrations of PRP formulations differentially affect the production of inflammatory mediators. Study Design Controlled laboratory study. Methods Peripheral blood was obtained from 4 donors and processed to create LR-PRP, LP-PRP, RBCs, and PPP. Human synoviocytes were cultured for 96 hours with the respective experimental conditions using standard laboratory conditions. Cell viability and inflammatory mediator production were then evaluated. Results Treatment with LR-PRP resulted in significantly greater synoviocyte death (4.9% ± 3.1%) compared with LP-PRP (0.72% ± 0.70%; P = .035), phosphate-buffered saline (PBS) (0.39% ± 0.27%; P = .018), and PPP (0.26% ± 0.30%; P = .013). Synoviocytes treated with RBC concentrate demonstrated significantly greater cell death (12.5% ± 6.9%) compared with PBS (P < .001), PPP (P < .001), LP-PRP (P < .001), and LR-PRP (4.9% ± 3.1%; P < .001). Interleukin (IL)–1β content was significantly higher in cultures treated with LR-PRP (1.53 ± 0.86 pg/mL) compared with those treated with PBS (0.22 ± 0.295 pg/mL; P < .001), PPP (0.11 ± 0.179 pg/mL; P < .001), and RBCs (0.64 ± 0.58 pg/mL; P = .001). IL-6 content was also higher with LR-PRP (32,097.82 ± 22,844.300 pg/mL) treatment in all other groups (P <.001). Tumor necrosis factor–α levels were greatest in LP-PRP (9.97 ± 3.110 pg/mL), and this was significantly greater compared with all other culture conditions (P < .001). Interferon-γ levels were greatest in RBCs (64.34 ± 22.987 pg/mL) and significantly greater than all other culture conditions (P <.001). Conclusion Treatment of synovial cells with LR-PRP and RBCs resulted in significant cell death and proinflammatory mediator production. Clinical Relevance Clinicians should consider using leukocyte-poor, RBC-free formulations of PRP when administering intra-articularly.

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Section: Discussionsupporting

confidence: 84%

The Effect of Platelet-Rich Plasma Formulations and Blood Products on Human Synoviocytes

et al. 2014

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“…The combined effect of iron with an inflammatory signal is also demonstrated in haemophilic mice as cartilage destruction upon a joint bleed can be attenuated either by treatment with deferasirox, an iron chelator,99 or by an anti-inflammatory treatment with IL-4 and IL-10 100…”

Section: Preclinical Studies On the Effects Of Iron Versus Blood On Tmentioning

confidence: 99%

The detrimental effects of iron on the joint: a comparison between haemochromatosis and haemophilia

et al. 2015

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Joint damage due to (recurrent) joint bleeding in haemophilia causes major morbidity. Although the exact pathogenesis has not been fully elucidated, a central role for iron is hypothesised. Likewise, in hereditary haemochromatosis joint destruction is caused by iron overload. A comparison between these types of arthropathy could provide more insight in the influence of iron in inducing joint damage. A literature review was performed to compare both disorders with respect to their clinical and histological characteristics, and preclinical studies on the influence of iron on different joint components were reviewed. Similarities in the features of arthropathy in haemochromatosis and haemophilia are cartilage degeneration, subchondral bone changes with osteophyte and cyst formation, and osteoporosis. In both disorders synovial inflammation and proliferation are seen, although this is much more explicit in haemophilia. Other substantial differences are the age at onset, the occurrence of chondrocalcinosis radiographically and calcium pyrophosphate dihydrate deposition disease in haemochromatosis, and a rapid progression with joint deformity and neovascularisation in haemophilia. Preclinical studies demonstrate detrimental effects of iron to all components of the joint, resulting in synovial inflammation and hyperplasia, chondrocyte death, and impaired osteoblast function. These effects, particularly the synovial changes, are aggravated in the presence of a pro-inflammatory signal, which is prominent in haemophilic arthropathy and minimal in haemochromatosis. Additional research is needed to further specify the role of iron as a specific target in treating these types of arthropathy.

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“…Intra-articular injection of IL-4 was performed as has been described before [34]. Mice were anesthetized with 2.5% isoflurane in 100% oxygen at a flow rate of 1 L/minute.…”

Section: Intra-articular Injection Of Il-4mentioning

confidence: 99%

IL-4 Modulates Macrophage Polarization in Ankylosing Spondylitis

Lin

Qiu

Chen

2015

Cell Physiol Biochem

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Background/Aims: Osteoclasts (OC) originate from monocytes/macrophages and play a critical role in the development of ankylosing spondylitis (AS). Receptor activator of NF-kB ligand (RANKL) is critical for the differentiation and maturation of OC from monocytes/macrophages, the underlying mechanisms of which processes have not been completely elucidated. Interleukin 4 (IL-4) attenuates the pathogenesis of AS via ill-defined mechanisms. Methods: We used a proteoglycan-induced arthritis (PGIA) model in Balb/c mice to study AS in humans. We injected IL-4 into the articular cavity and evaluated its effects on PGIA by incidence of arthritis, clinical and pathological arthritis severity and PET tracer uptake. We isolated and analyzed the number and polarization of macrophages in the articular cavity before and after IL-4 treatment. We analyzed RANKL levels in macrophage subtypes. We then isolated bone-marrow derived macrophages and treated them with IL-4 in vitro, with or without histone deacetylase inhibitors trichostatin A (TSA), and then analyzed the polarization of cultured macrophages before and after IL-4 treatment and RANKL levels in macrophage subtypes. Results: IL-4 treatment decreased the incidence and severity of arthritis in a mouse AS model, and polarized macrophages from a classical M1 subtype to an M2 subtype in vivo and in vitro. RANKL was predominantly produced by M1, but not by M2 macrophages. IL-4-mediated inhibition of RANKL in macrophages was abolished by TSA. Conclusion: Our data suggest that the therapeutic effects of IL-4 on AS may result from a M1-to-M2 macrophage polarization and its inhibition of RANKL expression on macrophages, possibly through enhanced histone deacetylation.

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A single intra‐articular injection with IL‐4 plus IL‐10 ameliorates blood‐induced cartilage degeneration in haemophilic mice

Cited by 37 publications

References 33 publications

The Effect of Platelet-Rich Plasma Formulations and Blood Products on Human Synoviocytes

The Effect of Platelet-Rich Plasma Formulations and Blood Products on Human Synoviocytes

The detrimental effects of iron on the joint: a comparison between haemochromatosis and haemophilia

IL-4 Modulates Macrophage Polarization in Ankylosing Spondylitis

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