Suppression of Collagen-Induced Arthritis by an Angiogenesis Inhibitor, AGM-1470, in Combination with Cyclosporin: Reduction of Vascular Endothelial Growth Factor (VEGF)

Oliver, Stephen J.; Cheng, Tammy P.; Banquerigo, Mona Lisa; Brahn, Ernest

doi:10.1006/cimm.1995.9978

Cited by 86 publications

(61 citation statements)

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“…It is unlikely that the process of growth factor-induced neovascularization that occurs in the cornea is mediated by different biochemical events than pathologic angiogenesis in the inflamed joint. This inference is supported by a study documenting sustained elevation in circulating TNF␣ concentrations in conjunction with falling tissue levels of VEGF in arthritic rats treated with an angiogenic inhibitor (24). However, our data do not support this interpretation because PEG sTNFRI did not exhibit an anti-angiogenic effect whether applied in either the arthritic joint or the cornea.…”

Section: Discussioncontrasting

confidence: 63%

“…This treatment paradigm is supported by numerous animal studies demonstrating that antiangiogenic agents significantly suppress both the incidence and the severity of disease (23)(24)(25)(26)(27)(28)(29). The most efficient means of adding angiogenesis inhibitors to the clinical armamentarium for RA would be to determine whether current therapies exhibit anti-angiogenic properties.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous animal studies indicate that antiangiogenic treatments effectively reduce both the incidence and the severity of collagen-induced arthritis (CIA) (23)(24)(25)(26)(27) and adjuvant-induced arthritis (AIA) (28,29). The present study compared the antiangiogenic activities of anti-IL-1 and anti-TNF␣ biologic agents in conventional models of arthritis and vascular growth factor-induced neovascularization.…”

mentioning

confidence: 96%

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Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis

Coxon¹,

Bolon²,

Estrada³

et al. 2002

Arthritis & Rheumatism

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Objective. To assess the capacities of the cytokine inhibitors interleukin-1 receptor antagonist (IL-1Ra; anakinra) and PEGylated soluble tumor necrosis factor receptor I (PEG sTNFRI; pegsunercept) to suppress neovascularization.Methods. A corneal angiogenesis assay was performed by implanting nylon discs impregnated with an angiogenic stimulator (basic fibroblast growth factor or vascular endothelial growth factor) into one cornea of female Sprague-Dawley rats. Animals were treated with IL-1Ra or PEG sTNFRI for 7 days, after which new vessels were quantified. In a parallel study, male Lewis rats with mycobacteria-induced adjuvant-induced arthritis were treated with IL-1Ra or PEG sTNFRI for 7 days beginning at disease onset, after which scores for inflammation and bone erosion as well as capillary counts were acquired from sections of arthritic hind paws.Results. Treatment with IL-1Ra yielded a dosedependent reduction in growth factor-induced corneal angiogenesis, while PEG sTNFRI did not. IL-1Ra, but not PEG sTNFRI, significantly reduced the number of capillaries in arthritic paws, even though both anticytokines reduced inflammation and bone erosion to a similar degree.Conclusion. These data support a major role for IL-1, but not TNF␣, in angiogenesis and suggest that an additional antiarthritic mechanism afforded by IL-1 inhibitors, but not anti-TNF agents, is the suppression of the angiogenic component of pannus.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

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Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis

Coxon¹,

Bolon²,

Estrada³

et al. 2002

Arthritis & Rheumatism

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“…Monocyte-derived MMP-9 is also involved in sepsis (56). VEGF is involved in RA (57) and in collagen-induced arthritis (58). In addition, neovascularization, to which TNF-␣, MMP-2, MMP-9, and VEGF are important contributors, plays an important role in RA (58), AA (59), and DTH (60).…”

Section: Discussionmentioning

confidence: 99%

Cu/Zn Superoxide Dismutase Plays Important Role in Immune Response

Marikovsky

Ziv

Nevo³

et al. 2003

The Journal of Immunology

182

112

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Activation of macrophages leads to the secretion of cytokines and enzymes that shape the inflammatory response and increase metabolic processes. This, in turn, results in increased production of reactive oxygen species. The role of Cu/Zn superoxide dismutase (SOD-1), an important enzyme in cellular oxygen metabolism, was examined in activated peritoneal elicited macrophages (PEM) and in several inflammatory processes in vivo. LPS and TNF-α induced SOD-1 in PEM. SOD-1 induction by LPS was mainly via extracellular signal-regulated kinase-1 activation. Transgenic mice overexpressing SOD-1 demonstrated a significant increase in the release of TNF-α and of the metalloproteinases MMP-2 and MMP-9 from PEM. Disulfiram (DSF), an inhibitor of SOD-1, strongly inhibited the release of TNF-α, vascular endothelial growth factor, and MMP-2 and MMP-9 from cultured activated PEM. These effects were prevented by addition of antioxidants, further indicating involvement of reactive oxygen species. In vivo, transgenic mice overexpressing SOD-1 demonstrated a 4-fold increase in serum TNF-α levels and 2-fold stronger delayed-type hypersensitivity reaction as compared with control nontransgenic mice. Conversely, oral administration of DSF lowered TNF-α serum level by 4-fold, lowered the delayed-type hypersensitivity response in a dose-dependent manner, and significantly inhibited adjuvant arthritis in Lewis rats. The data suggest an important role for SOD-1 in inflammation, establish DSF as a potential inhibitor of inflammation, and raise the possibility that regulation of SOD-1 activity may be important in the treatment of immune-dependent pathologies.

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“…A fumagillin derivative AGM-1470, toxic to proliferative endothelial cells, decreased the severity in collageninduced arthritis in rats by reducing VEGF levels. 7,8 A recent report shows that a monoclonal antibody neutralizing VEGF decreased CIA if injected in the early phase of the disease. 9 All these data argue for a beneficial therapeutic approach targeting angiogenesis in arthritis.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated gene transfer of urokinase plasminogen inhibitor inhibits angiogenesis in experimental arthritis

Apparailly¹,

Bouquet

Millet³

et al. 2002

Gene Ther

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Suppression of Collagen-Induced Arthritis by an Angiogenesis Inhibitor, AGM-1470, in Combination with Cyclosporin: Reduction of Vascular Endothelial Growth Factor (VEGF)

Cited by 86 publications

References 0 publications

Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis

Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis

Cu/Zn Superoxide Dismutase Plays Important Role in Immune Response

Adenovirus-mediated gene transfer of urokinase plasminogen inhibitor inhibits angiogenesis in experimental arthritis

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