Walmsley, M. et al. Interleukin-10 inhibition of the progression of established collagen-induced arthritis. Arthritis Rheum. 39, 495−503
Kennedy Krieger Institute, Kennedy, California, United States Arthritis & Rheumatology
(Impact Factor: 7.76).
03/1996; 39(3):495-503. DOI: 10.1002/art.1780390318
Interleukin-10 (IL-10) is a potent inhibitor of the proinflammatory cytokines, including tumor necrosis factor alpha and IL-1, which are considered important in the pathogenesis of rheumatoid arthritis (RA). The study was undertaken to establish whether IL-10 can ameliorate arthritis in the collagen-induced arthritis (CIA) model of RA.
DBA/1 mice were immunized with bovine type II collagen in adjuvant, and treated daily after disease onset with recombinant murine IL-10 or with saline as a control. Mice were monitored for paw swelling and clinical score. Histologic analysis was also performed.
IL-10 treatment of established CIA inhibited paw swelling (P < 0.0001), as well as disease progression as defined by clinical score (P < 0.0002). Cartilage destruction, as assessed histologically, was reduced in IL-10-treated mice compared with controls (P < 0.01).
IL-10 suppresses established CIA, probably by inhibiting proinflammatory cytokine production. Our results, taken together with previously reported findings, indicate a potential therapeutic role for IL-10 in RA.
Available from: Mathilde Boucard-Jourdin
- "IL-10 has been described as the main mediator of Tr1 anti-inflammatory effects. Systemic and locally administered IL-10 have previously been reported to have clear therapeutic potency in CIA
[44-50]. Interestingly, in those studies, the therapeutic effect of IL-10 on anti–Col II antibodies was associated with contradictory results that could be explained by the dose and timing of the IL-10 treatments. "
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Regulatory T (Treg) cells play a crucial role in preventing autoimmune diseases and are an ideal target for the development of therapies designed to suppress inflammation in an antigen-specific manner. Type 1 regulatory T (Tr1) cells are defined by their capacity to produce high levels of interleukin 10 (IL-10), which contributes to their ability to suppress pathological immune responses in several settings. The aim of this study was to evaluate the therapeutic potential of collagen type II–specific Tr1 (Col-Treg) cells in two models of rheumatoid arthritis (RA) in mice.
Col-Treg clones were isolated and expanded from collagen-specific TCR transgenic mice. Their cytokine secretion profile and phenotype characterization were studied. The therapeutic potential of Col-Treg cells was evaluated after adoptive transfer in collagen-antibody– and collagen-induced arthritis models. The in vivo suppressive mechanism of Col-Treg clones on effector T-cell proliferation was also investigated.
Col-Treg clones are characterized by their specific cytokine profile (IL-10highIL-4negIFN-γint) and mediate contact-independent immune suppression. They also share with natural Tregs high expression of GITR, CD39 and granzyme B. A single infusion of Col-Treg cells reduced the incidence and clinical symptoms of arthritis in both preventive and curative settings, with a significant impact on collagen type II antibodies. Importantly, injection of antigen-specific Tr1 cells decreased the proliferation of antigen-specific effector T cells in vivo significantly.
Our results demonstrate the therapeutic potential of Col-Treg cells in two models of RA, providing evidence that Col-Treg could be an efficient cell-based therapy for RA patients whose disease is refractory to current treatments.
Available from: Andrea Farini
- "In contrast this treatment increased the production of IL-10. Together with its well-known function as an anti-inflammatory factor , recent findings demonstrated that IL-10 is fundamental for the development of Tregs that control self-antigen–reactive T cells and induce peripheral tolerance in vivo . Interestingly, they found that treated mice had an increase in the percentage of CD4+ CD25+ FoxP3+ Tregs and suggested that these cells could migrate to the joints, regulating the suppression of the self-reactive response . "
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ABSTRACT: Extraordinary progress in understanding several key features of stem cells has been made in the last ten years, including definition of the niche, and identification of signals regulating mobilization and homing as well as partial understanding of the mechanisms controlling self-renewal, commitment, and differentiation. This progress produced invaluable tools for the development of rational cell therapy protocols that have yielded positive results in preclinical models of genetic and acquired diseases and, in several cases, have entered clinical experimentation with positive outcome. Adult mesenchymal stem cells (MSCs) are nonhematopoietic cells with multilineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. It is obvious that much work remains to be done to increase our knowledge of the mechanisms regulating development, homeostasis, and tissue repair and thus to provide new tools to implement the efficacy of cell therapy trials.
Available from: Yi-Seong Kwak
- "In line with this study, cytokines are implicated in each phase of the pathogenesis of rheumatoid arthritis, by promoting autoimmunity (during the prearticular phase), by maintaining chronic inflammatory synovitis and by driving the destruction of adjacent joint tissue . IL10 and IL-4 have been recognized as signature cytokines of Th2 cells that exert regulatory functions and are involved in the restoration of the immune tolerance . Cytokines, therefore, integrate the immunoregulatory and tissue-destructive events that underlie the clinical presentation and progression of rheumatoid arthritis, and thus those therapeutic agents regulating the cytokine profiles in RA are believed to be the drugs of choice . "
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ABSTRACT: Despite a multitude of reports on anti-inflammatory properties of ginseng extracts or individual ginsenosides, data on antiarthritic effect of ginseng saponin preparation with mixed ginsenosides is limited. On the other hand, a combined therapy of safe and inexpensive plant-derived natural products such as ginsenosides can be considered as an alternative to treat arthritis. Our previous in vitro data displayed a strong anti-inflammatory action of red ginseng saponin fraction-A (RGSF-A). We, herein, report a marked antiarthritic property of RGSF-A rich in ginsenoside Rb1, Rc, and Rb2. Collagen-induced arthritic (CIA) mice were treated with RGSF-A or methotrexate (MTX) for 5 weeks. Joint pathology, serum antibody production and leukocye activation, cytokine production in the circulation, lymph nodes, and joints were examined. RGSF-A markedly reduced severity of arthritis, cellular infiltration, and cartilage damage. It suppressed CD3(+)/CD69(+), CD4(+)/CD25(+), CD8(+) T-cell, CD19(+), B220/CD23(+) B-cell, MHCII(+)/CD11c(+), and Gr-1(+)/CD11b(+) cell activations. It further suppressed anti-CII- or anti-RF-IgG/IgM, TNF- α , IL-1 β , IL-17, and IL-6 secretions but stimulated IL-10 levels in the serum, joint, or splenocyte. RGSF-A attenuated arthritis severity, modified leukocyte activations, and restored cytokine imbalances, suggesting that it can be considered as an antiarthritic agent with the capacity to ameliorate the immune and inflammatory responses in CIA mice.
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