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

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Abstract
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 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 TNFα, 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.