The role of cytokines in angiogenesis.

Using the corneal model of neovascularization developed in their laboratory, the authors investigated the angiogenic potential of interleukin-1 (IL-1α and β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNFα), transforming growth factor β (TGFβ), granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon (IFN(γ) and IFN(γ)). Various concentrations of the tested cytokine were sequestered into Elvax-40 and implanted at 2.5 mm from the limbus within the corneal stroma of the rabbit eye. Three distinct groups of cytokines could be observed according to their angiogenic potential in this system. IL-1α was by far the most potent stimulator of neovascularization, inducing this process at concentrations as low as one nanogram per implant. TGFβ, TNFα and GM-CSF induced significant neovascularization only at concentrations of 500 nanograms per implant. IL-2, IL-6, IL-8, IFNα and IFN(γ) did not induce any significant neovascularization at the concentration tested (0.5 μg to 10 μg per implant).