The inability to restrain ongoing inflammation during EAE in GFAPcR1D mice was evident at multiple levels. Astrocyte activation was sustained consistent with increased expression of GFAP mRNA. CCL2, CCL5 and CXCL10 mRNA levels were increased (Fig. 8C ). The expression of mRNA encoding potentially destructive immune mediators including IL-1, IL-6, iNOS, and TNF were all increased (Fig. 8C ). IFN-c was ,2-fold higher in the CNS of GFAPcR1D mice (Fig. 9) . Lastly, the level of the antiinflammatory cytokine IL-10 was reduced ( Fig. 9 ), suggesting limited availability of IL-10 may be a key in prolonging astrocyte activation and inflammation [22] . A possible link between reduced IL-10 and the inability of IFN-c signaling to astrocytes is provided by the capacity of IFN-c to induce IL-27 in astrocytes [23] , thereby promoting IL-10 production. Indeed IL-27 in the CNS of the GFAPcR1D mice was significantly reduced compared to wt mice during chronic disease (Fig. 9 ). By contrast, IL-12 ( Fig. 9) , an indirect suppressor of CNS inflammation by promoting IFN-c production [24] , was similar in the CNS of both GFAPcR1D and wt mice. Astrocytes derived from GFAPcR1D and wt mice were stimulated with IFN-c to confirm IFN-c dependent IL-27 secretion by astrocytes [25] . While IFN-c induced IL-27 secretion by astrocytes from wt mice, IL-27 secretion was significantly reduced in cultures derived from GFAPcR1D mice (Fig. 10) . These data support the possibility that IFN-c mediated IL-27 secretion by astrocytes regulates EAE effector T cell function, inflammation and tissue destruction via induction of IL-10; however, this does not exclude the possibility that the inability of astrocytes to respond to IFN-c could directly or indirectly dysregulate a variety of other immunomodulatory functions [4, 5, 17] .