50-52 Figure 1 may help to understand the balance between Th1 and Th2. Figure 1. The balance between Th1 (cell-mediated) and Th2 (humoral) selleckchem response of the adaptive (specific) immune system. IL, interleukin; IFN-γ, interferon gamma; Th1 , T helper 1; Th2, T helper 2. Such a polarized

development of T cells happens not only on the Inhibitors,research,lifescience,medical peripheral level, but also in the CNS. Although initiation of T-cell responses is unlikely to occur within the CNS, T cells and monocytes will be massively recruited if pathogens are placed into the cerebral ventricles.53 Perivascular macrophages, owing to their location close to the definitely blood-brain barrier (BBB), can stimulate T cells to proliferate and secrete Th1 cytokines.54 Following Inhibitors,research,lifescience,medical extravasation into the CNS parenchyma,

T cells also interact with intrinsic CNS cells, particularly microglia and astrocytes.53 Microglia progressively acquire a clear-cut macrophage phenotype in response to CNS injuries,55 and can induce the production of Th1 cytokine IL-1256,57 and of Th2 cytokines such as IL-10 and TGFβ.53 Astrocytes are also potential sources of TGFβ, Inhibitors,research,lifescience,medical which inhibits MHC II (major histocompatibility complex II) and ICAM-1 (intercellular adhesion molecule 1) expression in macrophage/microglia.58 Microglia and astrocytes also secrete chemokines that may affect the recruitment of Th1 and Th2 cells. In sum, a complex network between microglia, astrocytes, and T cells is involved in the balance between Th1 and Th2 systems, which in turn might have impact on immune responses within the CNS. How do cytokines act on the CNS? Five ways for cytokine signals to enter the brain One of the major reasons why the brain has long been Inhibitors,research,lifescience,medical defined as an immunologically privileged organ is the presence of a tight barrier between the brain and the periphery: the BBB. To our current knowledge, there are five pathways via which cytokine signals may cross the BBB. Transport across the BBB There is evidence for an active, Inhibitors,research,lifescience,medical saturable, and specific transport system for certain cytokines across the BBB. By the use of radiolabeled cytokines in animal experiments,

Entinostat cytokines like IL-1, TNF-α, and IL-2 were demonstrated to be transported across the BBB.59-62 These experiments suggest that active transport plays a significant role in getting cytokines across the BBB. One limitation, however, is that the absorption of labeled cytokines into the brain tissue may not reflect the transport of cytokines across the BBB, but the binding of cytokines to the BBB. Some data show that the majority of intravenously (IV) infused radiolabeled IL-1α can be found on brain endothelial cells,63 or on the surface and pinocytotic vesicles of the brain endothelia shortly after injection.64 Passage of circumventricular organs The second pathway is that cytokines may affect the C the circumventricular organs (CVOs), which possess a leaky BBB.