Ligands for the peroxisome proliferator-activated receptor-γ and the retinoid X receptor exert additive anti-inflammatory effects on experimental autoimmune encephalomyelitis

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) is a member of the nuclear-receptor superfamily that binds to DNA with retinoid X receptors (RXRs) as PPAR–RXR heterodimers. In experimental autoimmune encephalomyelitis (EAE), the gene expression of PPAR-γ was demonstrated in spinal cord during the course of EAE. Administration of 15-deoxy- 12,14-prostaglandin J2 (15d-PGJ2) or 9- cis-retinoic acid (RA) alone at the onset of clinical signs of EAE reduced the severity of disease, however, their combination resulted in enhanced amelioration of disease. These results suggest that use of RXR specific ligands may be highly effective when combined with PPAR-γ agonists in the treatment of autoimmune demyelinating diseases such as multiple sclerosis (MS).