Interleukin-2 does not cross the blood-brain barrier by a saturable transport system

Blood-borne interleukin-2 (IL-2), like other cytokines, is known to affect the central nervous system (CNS). One mechanism by which circulating substances can alter brain function is to directly cross the blood-brain barrier (BBB). We investigated the ability of IL-2 to cross the BBB, the interface between the periphery and the CNS. IL-2 labeled with 125I (I-IL-2) was injected into mice intravenously and its rate of entry into the brain determined by multiple-time regression analysis. I-IL-2 was found to enter the brain about 10 times faster than albumin. Neither morphine nor antibodies to IL-2, IL-1 alpha, or the IL-1 receptor affected the entry of I-IL-2. High performance liquid chromatography (HPLC) confirmed that the radioactivity entering the brain represented intact cytokine. However, excess unlabeled IL-2 was unable to impede the entry of I-IL-2, indicating that this transport is nonsaturable. This contrasts with saturable transport systems found for the cytokines IL-1 alpha and TNF-alpha, but still may explain how IL-2 can exert central effects.