Regulation of eae using the growth factors TGF-β and IGF-1. MK

The presence of the growth factors, transforming growth factor-β (TGF-β) and insulin-like growth factor-1 (IGF-1), in the central nervous system (CNS) of mice with experimental allergic encephalomyelitis (EAE) implicates these molecules in disease pathogenesis, and suggests their potential therapeutic use. The adoptive transfer model of EAE allows the investigation of the activation of encephalitogenic T cells in vitro and the mechanisms involved in the production of EAE in vivo. The presence of TGF-β during in vitro T cell activation inhibited T cell proliferation and encephalitogenicity prior to adoptive transfer, while IGF-1/IGF binding protein (BP)3 complex enhanced proliferation of T cells. The presence of these growth factors in vitro also altered the production of cytokines important in disease pathogenesis. Following the transfer of encephalitogenic T cells, administration of either TGF-β or IGF-1/ IGFBP3 to mice prior to the onset of disease resulted in delayed onset and a dramatic reduction in CNS inflammation. These results suggest that growth factors such as TGF-β and IGF-1 can affect disease outcome in EAE by their effects both on immune cells and at the target organ, the CNS.