Increased serum levels of IL-2 and sIL-2R can be demonstrated in patients with active MS, a finding that strongly supports the hypothesis of a systemic T cell activation in such patients. However, IL-2 may play a crucial role in MS immunopathology by activating endothelial cells, as suggested by the vascular leak syndrome complicating hrIL-2 therapy. Early BBB impairment and focal perivascular edema that characterize MS lesions may be the effect of an IL-2-induced cytokine cascade.