Interleukin‐10 inhibition of the progression of established collagen‐induced arthritis

Walmsley, Marita J.; Katsikis, Peter D.; Abney, Erika R.; Parry, Sarah; Williams, Richard O.; Maini, R. N.; Feldmann, Marc

doi:10.1002/art.1780390318

Cited by 246 publications

(168 citation statements)

References 46 publications

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“…Intraarticular administration of IL-10 did not reduce the severity of arthritis (34), whereas systemic injection with recombinant IL-10 effectively inhibited disease (36). We detected a higher proportion of IL-10-producing T cells in the spleen after tolerogenic DC treatment, suggesting a systemic increase in IL-10.…”

Section: Discussionmentioning

confidence: 66%

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Stoop¹,

Harry²,

Delwig³

et al. 2010

Arthritis & Rheumatism

124

114

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Results. Tolerogenic DCs displayed a semimature phenotype, produced low levels of inflammatory cytokines, and exhibited low T cell stimulatory capacity. Upon intravenous injection into arthritic mice, tolerogenic DCs migrated to the spleen, liver, lung, feet, and draining lymph nodes. Treatment of arthritic mice with type II collagen-pulsed tolerogenic DCs, but not unpulsed tolerogenic DCs or mature DCs, significantly inhibited disease severity and progression. This improvement coincided with a significant decrease in the number of Th17 cells and an increase in the number of interleukin-10-producing CD4؉ T cells, whereas tolerogenic DC treatment had no detectable effect on Th1 cells or interleukin-17-producing ␥/␦ T cells.Conclusion. Treatment with type II collagenpulsed tolerogenic DCs decreases the proportion of Th17 cells in arthritic mice and simultaneously reduces the severity and progression of arthritis.

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Section: Discussionmentioning

confidence: 66%

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Stoop¹,

Harry²,

Delwig³

et al. 2010

Arthritis & Rheumatism

124

114

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“…However, these studies showed different results regarding humoral immune responses to collagen type II (CII). In our laboratory no significant differences in the Ab profile between controls and IL-10-injected animals has been observed over the 10-day treatment period (7). On the contrary, other investigators found a reduction of autoantibodies to CII in rat collagen-induced arthritis (CIA) when IL-10 was administered systemically and an increase when it was injected locally in the paws (8).…”

mentioning

confidence: 61%

Murine IL-10 Gene Transfer Inhibits Established Collagen-Induced Arthritis and Reduces Adenovirus-Mediated Inflammatory Responses in Mouse Liver

Quattrocchi

Dallman

Dhillon

et al. 2001

The Journal of Immunology

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The effects of homologous IL-10 administration during an established autoimmune disease are controversial, given its reported immunostimulatory and immunosuppressive properties. Studies of collagen-induced arthritis have shown efficacy with repeated administrations of IL-10; however, when the EBV IL-10 homologue was administered via adenovirus gene transfer technology the results were equivocal. Therefore, the present study was undertaken to elucidate the effects of prolonged homologous IL-10 administration via adenovirus-mediated gene delivery on the progression of established arthritis. Collagen type II (CII)-immunized mice received i.v. injections of 107 or 108 PFU of an E1-deleted adenoviral vector containing the murine IL-10 gene (AdIL-10), after arthritis onset. Mice were monitored for 3 wk for disease progression, and gene transduction was assessed by quantification of serum mIL-10. CII-specific cell-mediated and humoral immune responses were analyzed by lymph node cell proliferation, cytokine production, and anti-CII Ab responses. Furthermore, because adenoviral vectors have been reported to induce organ dysfunction due to cell-mediated immune responses to the viral Ags, we have also evaluated delayed-type hypersensitivity responses and reactive hepatitis to the systemically delivered adenovirus and whether the IL-10 produced could influence those responses. Sustained suppression of autoimmune arthritis and elevated serum levels of IL-10 were achieved in our study. AdIL-10 treatment reduced cell-mediated immune reactivity, but did not affect humoral responses. Furthermore, IL-10 was able to reduce, but not totally abrogate, adenovirus-induced hepatic inflammation. These findings provide further insights into the diverse interplay of immune processes involved in autoimmune inflammation and the mechanism of cytokine immunotherapy.

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“…In many cases, their precise roles are, as yet, incompletely defined. A growing body of evidence from both animal models of arthritis and human RA suggests that Th2-type cytokines, such as IL-4 and IL-10, can protect against arthritis, whereas Th1-type cytokines, such as IL-2 and IFN-␥, can be pro-inflammatory (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Heterogeneous Effects Of Il-2 Onmentioning

confidence: 99%

Heterogeneous Effects of IL-2 on Collagen-Induced Arthritis

Thornton

Boivin

Kim

et al. 2000

The Journal of Immunology

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IL-2 is generally considered a pro-inflammatory cytokine that exacerbates Th1-mediated disease states, such as autoimmune arthritis. Consistent with this role for IL-2, recent studies from our laboratory demonstrate that IL-2 mRNA is markedly increased during the acute stage of collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. To further define the role of IL-2 in CIA, the levels of IL-2 protein and its receptor and the effects of IL-2 administration were analyzed during CIA. IL-2 protein and IL-2R were preferentially expressed at disease onset, compared with later stages of disease. Administration of recombinant human IL-2 (rhIL-2) at, or just before, disease onset exacerbated disease; surprisingly, rhIL-2 given before disease onset inhibited CIA, associated with reduced cellular and humoral responses to type II collagen. Determination of in vivo serum levels of Th1 and Th2 cytokines in response to rhIL-2 treatment demonstrated that IFN-γ, but not IL-4, was markedly up-regulated in response to IL-2. In mice treated with anti-IFN-γ Ab, both early and late IL-2 administration exacerbated CIA. Thus, IL-2 can have two opposite effects on autoimmune arthritis, a direct stimulatory effect and an indirect suppressive effect that is mediated by IFN-γ.

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Interleukin‐10 inhibition of the progression of established collagen‐induced arthritis

Cited by 246 publications

References 46 publications

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Murine IL-10 Gene Transfer Inhibits Established Collagen-Induced Arthritis and Reduces Adenovirus-Mediated Inflammatory Responses in Mouse Liver

Heterogeneous Effects of IL-2 on Collagen-Induced Arthritis

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