Intravenous immunoglobulins (IVIg) preparations can be beneficial therapeutic agents for the treatment of tumor metastases as has been shown in both human and animal studies. Operating mechanisms have not yet been completely elucidated. Some of the mechanisms proposed entail the stimulation of the production of IL-12, a cytokine that exhibits anti-angiogenic activities, as well as inhibition of endothelial cells proliferation and vascular endothelial growth factor (VEGF) secretion. The aim of the present study was to investigate whether in an IVIg preparation there are natural antibodies directed against VEGF with the potential to affect angiogenesis. Using both sandwich and direct ELISA assays, IVIg was found to specifically recognize and bind VEGF in a dose-dependent manner. The binding specificity was confirmed by inhibition of IVIg binding to VEGF by VEGF as an inhibitor, as shown by ELISA and immunoblot. A mouse hind limb ischemia model was employed to evaluate the in vivo IVIg-induced inhibition of angiogenesis. IVIg was found to exhibit inhibitory effect on VEGF-mediated blood perfusion in the ischemic limb. The present study shows a presence of anti-VEGF fraction in IVIg preparation.
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