Treatment with gamma‐interferon triggers the onset of collagen arthritis in mice

Mauritz, Nils Johan; Holmdahl, Rikard; Jönsson, Roland; Meide, Peter H. Der Van; Scheynius, Annika; Klareskog, Lars

doi:10.1002/art.1780311012

Cited by 146 publications

(82 citation statements)

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“…The RA synovium is infiltrated with CD4 ϩ T cells of the Th1 phenotype (13). In murine collagen-induced arthritis (CIA), a model of RA, administration of IFN-␥ can exacerbate disease (14,15), and administration of anti-IL-2R Abs can inhibit disease onset (16). Thus, it is surprising that most studies of cytokines in RA have failed to detect IL-2 protein in RA synovial fluid (17).…”

Section: Heterogeneous Effects Of Il-2 Onmentioning

confidence: 99%

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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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Section: Heterogeneous Effects Of Il-2 Onmentioning

confidence: 99%

“…Analysis of the role of IFN-␥ in animal models of arthritis have suggested both protective and exacerbating effects of IFN-␥ on disease (14,15,(45)(46)(47)(48). Interestingly, administration of IFN-␥ has been shown to protect or exacerbate disease in rat adjuvant arthritis, depending on the time of administration (49).…”

Section: Figurementioning

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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“…Considerable data have been accumulated to suggest that a Th1 environment is required for the induction of a proinflammatory anticollagen T cell response and induction of complement-fixing anticollagen antibodies, of the IgG2a isotype, which are essential for the development of CIA (15)(16)(17). In contrast, Th2-associated cytokines, such as IL-4 and IL-10, are associated with the remission phase of CIA (18).…”

mentioning

confidence: 99%

Treatment of murine collagen‐induced arthritis by the stress protein BiP via interleukin‐4–producing regulatory T cells: A novel function for an ancient protein

Brownlie

Myers

Wooley

et al. 2006

Arthritis & Rheumatism

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Objective. Following the demonstration that the stress protein, BiP, prevented induction of collageninduced arthritis (CIA) in HLA-DRB*0101 ؉/؉ (HLA-DR1 ؉/؉ ) mice, we investigated the immunotherapeutic ability of BiP to suppress disease during the active phase of CIA in HLA-DR1 ؉/؉ and DBA/1 mice.Methods. BiP was administered either subcutaneously or intravenously to DBA/1, HLA-DR1 ؉/؉ , or interleukin-4 (IL-4)-knockout mice at the onset of arthritis. Immune cells were used in adoptive transfer studies or were restimulated in culture with BiP or type II collagen (CII). Proliferation and cytokine release were measured. In addition, serum anti-CII antibodies were measured by enzyme-linked immunosorbent assay. Disease progression was scored using a visual analog scale.Results. BiP was successful in suppressing estab-

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“…However, IFNy has several other properties which might make it an effective antiarthritic agent, including its ability to inhibit B cell activation and cytokine production by macrophages and monocytes, as well as its antiproliferative effects. Not surprisingly, there are conflicting reports, from studies using animal models of arthritis, regarding whether treatment with IFNy resulted in worsening or improvement of disease (80,81). Several uncontrolled as well as double-blind placebocontrolled trials to determine the efficacy of recombinant IFNy for the treatment of RA have been completed (82)(83)(84)(85).…”

Section: Cytokine Targetsmentioning

confidence: 99%