The inflammatory response in experimental autoimmune encephalomyelitis is redirected from the spinal cord to the cerebellum in transgenic mice with astrocyte production of IL-6

Interleukin (IL)-6 is essential for the induction of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Recent studies further demonstrated that IL-6 is involved in the generation of Th17 T-cells, which mediate the tissue damage during EAE. To further clarify the role of IL-6 in EAE, we examined transgenic mice with astrocyte and predominantly cerebellar but not spinal cord production of IL-6 (GF-IL6) after active immunization with myelin oligodendrocyte glycoprotein (MOG). MOG-immunized (Mi-) GF-IL6 mice developed severe ataxia but no clinical signs of spinal inflammation, which was in sharp contrast to Mi-wild type (WT) animals that developed hind limb paralysis. Histological examination revealed severe inflammation and demyelination in the cerebellum but not in the spinal cord of Mi-GF-IL6 mice. Cerebellar tissue damage was accompanied by an increase of T cells, macrophages and neutrophils at peak disease. Furthermore, the amount of apoptotic T-cells was increased 2.5fold in the cerebellum of GF-IL6 mice. Proinflammatory cytokines (IFNgamma, TNF, IL-17) were found at comparable levels in both Mi-GF-IL6 and Mi-WT cerebellum, whereas higher levels were found in Mi-WT spinal cord. Induction of EAE in mice after a cerebral cryolesion and in transgenic mice with an astrocyte IL-12-production, induced typical spinal cord inflammation arguing for a specific role of IL-6 in the observed course of EAE. Our findings suggest that the IL-6 primed cerebellum acts as a homing “sink“ for MOG-reactive T cells in EAE, which subsequently by-pass the spinal cord and undergo apoptosis.