The Th1/Th2 cytokine balance in arthritis

Miossec, Pierre

doi:10.1007/978-3-0348-8823-3_5

Cited by 41 publications

(52 citation statements)

References 81 publications

(26 reference statements)

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“…Proinflammatory cytokines, such as IL‐1 and TNFα, have been shown to be pivotal in the pathogenesis and progression of the disease and have been successfully targeted in the treatment of RA patients (31). An imbalance of Th1/Th2 cytokines is likely to impact the chronic inflammation associated with RA (32), with IL‐4 playing a critical role in the Th2 reaction and able to modulate the IL‐1– and TNFα‐mediated inflammatory responses (33, 34).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of angiogenesis by interleukin‐4 gene therapy in rat adjuvant‐induced arthritis

Haas¹,

Amin²,

Allen³

et al. 2006

Arthritis & Rheumatism

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Objective. Interleukin-4 (IL-4) can modulate neovascularization. In this study, we used a gene therapy approach to investigate the role of IL-4 in angiogenesis in rat adjuvant-induced arthritis (AIA), a model for rheumatoid arthritis.Methods. Rats received an adenovirus producing IL-4 (AxCAIL-4), a control virus without insert, or control vehicle (phosphate buffered saline) intraarticularly before arthritis onset. At peak onset of arthritis, rats were killed. Vascularization was determined in the synovial tissue, and correlations with inflammation were assessed. Ankle homogenates were used in angiogenesis assays in vitro and in vivo, and protein levels of cytokines and growth factors were assessed by enzymelinked immunosorbent assay. Synovial tissue expression of ␣v integrins was determined by immunohistochemistry.Results. IL-4 induced a reduction in synovial tissue vessel density, which was paralleled by a decrease in inflammation. AxCAIL-4 joint homogenates significantly (P < 0.05) inhibited both endothelial cell (EC) migration and tube formation in vitro. Similarly, AxCAIL-4 inhibited capillary sprouting in the rat aortic ring assay, and vessel growth in the in vivo Matrigel plug assay. The angiostatic effect occurred despite high levels of vascular endothelial growth factor (VEGF), and was associated with down-regulation of the proangiogenic cytokines IL-18, CXCL16, and CXCL5 and upregulation of the angiogenesis inhibitor endostatin. Of interest, AxCAIL-4 also resulted in decreased EC expression of the ␣v and ␤3 integrin chains.Conclusion. In rat AIA, IL-4 reduces synovial tissue vascularization via angiostatic effects, mediates inhibition of angiogenesis via an association with altered pro-and antiangiogenic cytokines, and may inhibit VEGF-mediated angiogenesis and exert its angiostatic role in part via ␣v␤3 integrin. This knowledge of the specific angiostatic effects of IL-4 may help optimize target-oriented treatment of inflammatory arthritis.

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Section: Discussionmentioning

confidence: 99%

Inhibition of angiogenesis by interleukin‐4 gene therapy in rat adjuvant‐induced arthritis

Haas¹,

Amin²,

Allen³

et al. 2006

Arthritis & Rheumatism

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“…There is also general agreement that Th1 cells are important mediators of pathology in organ‐specific autoimmune diseases. Although RA has a number of important systemic features, it is the chronic inflammation in the joints that is the most consistently destructive feature of the disease, and a number of studies have shown that T cells in RA joints are predominantly of a Th1 phenotype (1). Immunohistochemical analysis of arthritic joints reveals abundant expression of monocyte‐derived proinflammatory cytokines, which is also consistent with Th1‐mediated disease, and on this basis, it has been proposed that down‐regulation of the Th1 response would be beneficial in the treatment of RA.…”

Section: Discussionmentioning

confidence: 99%

“…Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis and progressive destruction of the joint. Although many questions concerning the etiology of RA remain unanswered, cumulative evidence suggests that CD4+ T cells, which exhibit a predominantly Th1 pattern of cytokine expression, play an important role in the pathogenesis of the disease (1).…”

mentioning

confidence: 99%

Down‐regulation of Th1‐mediated pathology in experimental arthritis by stimulation of the Th2 arm of the immune response

Mauri¹,

Feldmann²,

Williams³

2003

Arthritis & Rheumatism

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“…Because IL‐17 is a T cell product, it was logical to search for the position of IL‐17 in the now classic Th1/Th2 subsets (43). This classification is useful to understand cytokine patterns in relation to disease.…”

Section: Il‐17 and The Th1/th2 Cytokine Balancementioning

confidence: 99%

Interleukin‐17 in rheumatoid arthritis: If T cells were to contribute to inflammation and destruction through synergy

Miossec

2003

Arthritis & Rheumatism

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166

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The Th1/Th2 cytokine balance in arthritis

Cited by 41 publications

References 81 publications

Inhibition of angiogenesis by interleukin‐4 gene therapy in rat adjuvant‐induced arthritis

Inhibition of angiogenesis by interleukin‐4 gene therapy in rat adjuvant‐induced arthritis

Down‐regulation of Th1‐mediated pathology in experimental arthritis by stimulation of the Th2 arm of the immune response

Interleukin‐17 in rheumatoid arthritis: If T cells were to contribute to inflammation and destruction through synergy

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