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

被引：79

作者：

Coxon, A ^{[1
]}

Bolon, B ^{[1
]}

Estrada, J ^{[1
]}

Kaufman, S ^{[1
]}

Scully, S ^{[1
]}

Rattan, A ^{[1
]}

Duryea, D ^{[1
]}

Hu, YL ^{[1
]}

Rex, K ^{[1
]}

Pacheco, E ^{[1
]}

Van, G ^{[1
]}

Zack, D ^{[1
]}

Feige, U ^{[1
]}

机构：

[1] Amgen Inc, Thousand Oaks, CA 91320 USA

来源：

ARTHRITIS AND RHEUMATISM | 2002年 / 46卷 / 10期

关键词：

D O I：

10.1002/art.10546

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 sTNFR1; 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 dose-dependent 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 TNFalpha, 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.

引用

页码：2604 / 2612

页数：9

共 53 条

[21]

Jackson JR, 1997, J RHEUMATOL, V24, P1253

[22] Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice - A comparative study using anti-TNF alpha, anti-IL-1 alpha/beta, and IL-1Ra [J].