Research indicates that GW501516 and L-165041 are also effective at ameliorating EAE. In mice, the attenuation of EAE by GW501516 or L-165041 was associated with decreased expression of the proinflammatory cytokines, IL-2 and IL-23, and increased expression of the anti-inflammatory cytokines, IL-4 and IL-10. Reduced production of IFNγ and IL-17 by T helper type 1 (Th1) and Th17 cells was also observed in EAE mice treated with GW501516 or L-165041 [50]. In accord with these findings, PPARδ-null mice with EAE had impaired Th1/Th17 and Th2/Treg responses, which may contribute to the extended recovery time in PPARδ-null mice compared to WT mice. The prolonged EAE in PPARδ-null mice was associated with sustained levels of IFNγ, IL-17, IL-12p35, and IL-12p40, consistent with the hypothesis that PPARδ regulates inflammatory responses associated with EAE [19].
