Differential effects of interleukins 10 and 4 on the production of interleukin‐6 by blood and synovium monocytes in rheumatoid arthritis

Chomarat, Pascale; Banchereau, Jacques; Miossec, Pierre

doi:10.1002/art.1780380805

Cited by 51 publications

(20 citation statements)

References 31 publications

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“…Not all cytokines classified as antiinflammatory were able to block MIP-3␣ production; in particular, addition of IL-10 had no effect on the production of MIP-3␣ by RA synovium and RA synoviocytes stimulated with cytokines. This finding could be related to the elevated levels of endogenous IL-10 locally produced by synovium monocytes (29,43). In keeping with this, IL-10 was found previously to have no effect on LIF or IL-6 production by isolated synoviocytes (26).…”

Section: Figuresupporting

confidence: 68%

Enhancing Effect of IL-1, IL-17, and TNF-α on Macrophage Inflammatory Protein-3α Production in Rheumatoid Arthritis: Regulation by Soluble Receptors and Th2 Cytokines

Chabaud

Page

Miossec

2001

The Journal of Immunology

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220

155

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Macrophage inflammatory protein (MIP)-3α is a chemokine involved in the migration of T cells and immature dendritic cells. To study the contribution of proinflammatory cytokines and chemokines to the recruitment of these cells in rheumatoid arthritis (RA) synovium, we looked at the effects of the monocyte-derived cytokines ΙL-1β and TNF-α and the T cell-derived cytokine IL-17 on MIP-3α production by RA synoviocytes. Addition of ΙL-1β, IL-17, and TNF-α induced MIP-3α production in a dose-dependent manner. At optimal concentrations, ΙL-1β (100 pg/ml) was much more potent than IL-17 (100 ng/ml) and TNF-α (100 ng/ml). When combined at lower concentrations, a synergistic effect was observed. Conversely, the anti-inflammatory cytokines IL-4 and IL-13 inhibited MIP-3α production by activated synoviocytes, but IL-10 had no effect. Synovium explants produced higher levels of MIP-3α in RA than osteoarthritis synovium. MIP-3α-producing cells were located in the lining layer and perivascular infiltrates in close association with CD1a immature dendritic cells. Addition of exogenous IL-17 or ΙL-1β to synovium explants increased MIP-3α production. Conversely, specific soluble receptors for ΙL-1β, IL-17, and TNF-α inhibited MIP-3α production to various degrees, but 95% inhibition was obtained only when the three receptors were combined. Similar optimal inhibition was also obtained with IL-4, but IL-13 and IL-10 were less active. These findings indicate that interactions between monocyte and Th1 cell-derived cytokines contribute to the recruitment of T cells and dendritic cells by enhancing the production of MIP-3α by synoviocytes. The inhibitory effect observed with cytokine-specific inhibitors and Th2 cytokines may have therapeutic applications.

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Section: Figuresupporting

confidence: 68%

Enhancing Effect of IL-1, IL-17, and TNF-α on Macrophage Inflammatory Protein-3α Production in Rheumatoid Arthritis: Regulation by Soluble Receptors and Th2 Cytokines

Chabaud

Page

Miossec

2001

The Journal of Immunology

Self Cite

220

155

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“…Addition of exogenous IL-4 to cultures of RA synovial tissue cells or synovial tissue explants suppresses synthesis of pro-inflammatory cytokines such as IL-6, IL-1, TNF-␣, and GM-CSF as well as metalloproteinases. [26][27][28] These activities might be related to either suppression of Th1 function or a direct effect on synoviocytes and macrophages in RA. Furthermore, the potential usefulness of Th2 cytokines in RA is supported by the observation that T cell clones from rheumatoid joints tend to exhibit a Th1 phenotype.…”

Section: Discussionmentioning

confidence: 99%

Intra-articular IL-4 gene therapy in arthritis: anti-inflammatory effect and enhanced Th2activity

Boyle¹,

Nguyen²,

Zhuang³

et al. 1999

Gene Ther

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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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Differential effects of interleukins 10 and 4 on the production of interleukin‐6 by blood and synovium monocytes in rheumatoid arthritis

Cited by 51 publications

References 31 publications

Enhancing Effect of IL-1, IL-17, and TNF-α on Macrophage Inflammatory Protein-3α Production in Rheumatoid Arthritis: Regulation by Soluble Receptors and Th2 Cytokines

Enhancing Effect of IL-1, IL-17, and TNF-α on Macrophage Inflammatory Protein-3α Production in Rheumatoid Arthritis: Regulation by Soluble Receptors and Th2 Cytokines

Intra-articular IL-4 gene therapy in arthritis: anti-inflammatory effect and enhanced Th2activity

Heterogeneous Effects of IL-2 on Collagen-Induced Arthritis

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