To further examine the mechanisms by which PPARδ is protective in models of EAE, studies have used in vitro models of aggregating brain cells. GW501516 was effective at reducing IFN-γ- or lipopolysaccharide- (LPS-) induced TNF-α or inducible nitric oxide synthase (iNOS) mRNA levels; however, it increased IL-6 mRNA expression. In the presence of anti-MOG, a demyelinating antibody, GW501516 was unable to prevent decreases in MBP [54]. These results further suggest that in models of EAE, the protective effects of PPARδ agonists may be due to their anti-inflammatory properties rather than their effects on myelin genes or oligodendrocytes. Collectively, the findings above indicate that PPARδ agonists ameliorate the inflammatory responses in EAE and may represent therapeutic avenues to ameliorate MS progression.
