Heterogeneous Effects of IL-2 on Collagen-Induced Arthritis

Thornton, Sherry; Boivin, Gregory P.; Kim, Kwang N.; Finkelman, Fred D.; Hirsch, Raphael

doi:10.4049/jimmunol.165.3.1557

Cited by 51 publications

(48 citation statements)

References 53 publications

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“…Unexpectedly, the onset of arthritis was delayed in mice pretreated with anti-IL-2 ( Figure 2D). This finding is most likely due to the loss of IL-2 itself and is consistent with the previously reported observation that administration of recombinant human IL-2 at the onset of disease exacerbates CIA (19). However, following the onset of disease, the severity of arthritis is markedly enhanced in mice pretreated with anti-IL-2.…”

supporting

confidence: 82%

Interleukin‐6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses

Fujimoto¹,

Serada²,

Mihara³

et al. 2008

Arthritis & Rheumatism

213

141

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Conclusion. Our results indicate that the protective effect of IL-6 blockade, but not tumor necrosis factor (TNF) blockade, in CIA correlates with the inhibition of Th17 differentiation. Our findings suggest that IL-6 blockade in rheumatoid arthritis in human is also likely to involve a therapeutic mechanism distinct from that of TNF blockade and thus may represent an alternative therapy for patients in whom the disease is refractory to TNF blockade.

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supporting

confidence: 82%

Interleukin‐6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses

Fujimoto¹,

Serada²,

Mihara³

et al. 2008

Arthritis & Rheumatism

213

141

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“…The IL-2-induced IFN-␥ production and Th1 differentiation by NOD T cells, in vitro, support the existence of such a pathway. Consistent with this view, it has been shown that injection of human rIL-2 into DBA/1 mice, an animal model of rheumatoid arthritis, results in markedly increased IFN-␥ production, in vivo (29). The comparable levels of IL-2 production and IL-2R expression by NOD and B6 CD4 ϩ T cells suggest that signaling downstream of IL-2/IL-2R engagement plays a role in the IL-2-induced Th1 differentiation.…”

Section: Cd44supporting

confidence: 60%

Either IL-2 or IL-12 Is Sufficient to Direct Th1 Differentiation by Nonobese Diabetic T Cells

Zhou

Zhang

Aune

2003

The Journal of Immunology

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Th cell differentiation from naive precursors is a tightly controlled process; the most critical differentiation factor is the action of the driving cytokine: IL-12 for Th1 development, IL-4 for Th2 development. We found that CD4+ T cells from nonobese diabetic mice spontaneously differentiate into IFN-γ-producing Th1 cells in response to polyclonal TCR stimulation in the absence of IL-12 and IFN-γ. Instead, IL-2 was necessary and sufficient to direct T cell differentiation to the Th1 lineage by nonobese diabetic CD4+ T cells. Its ability to direct Th1 differentiation of both naive and memory CD4+ T cells was clearly uncoupled from its ability to stimulate cell division. Autocrine IL-2-driven Th1 differentiation of nonobese diabetic T cells may represent a genetic liability that favors development of IFN-γ-producing autoreactive T cells.

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“…A growing body of evidence suggests that Th1 responses are predominant in the development of murine CIA (2). It has been reported that IL-2 can play an antiinflammatory role during early phases of CIA induction, but is proinflammatory in established disease (32). Previous studies have demonstrated that carbon monoxide inhibits T cell proliferation and IL-2 secretion (33), and biliverdin has been shown to inhibit IL-2 transcription and T cell proliferation in a murine model of heart transplantation (15).…”

Section: Discussionmentioning

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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Heterogeneous Effects of IL-2 on Collagen-Induced Arthritis

Cited by 51 publications

References 53 publications

Interleukin‐6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses

Interleukin‐6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses

Either IL-2 or IL-12 Is Sufficient to Direct Th1 Differentiation by Nonobese Diabetic T Cells

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

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