Lovastatin exhibits synergy with Vitamin D hormone to confer protection from experimental autoimmune encephalomylitis (148.5)

Abstract

Abstract Recent studies provide sufficient evidence that disease modifying agents (DMAs) i.e., vitamin D hormone (VDH) and statin (lovastatin) were immunomodulatory to attenuate experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Interestingly, irrespective of their different mechanism of action these DMAs produce similar protective activities to attenuate EAE. Therefore, we asked whether statin regulate the vitamin D precursor (VDP; vitamin D3) homeostasis in treated EAE model. Interestingly, we observed a significant increase in the serum level of both VDP and VDH in lovastatin treated EAE animals as compared to those treated with vehicle. It was associated with diminished level of CYP24A1 (VDH inactivating enzyme) and elevated level of CYP27B1 (VDH synthesizing enzyme) involved in VDH metabolism in the blood cells and spinal cord of EAE treated with lovastatin than vehicle. Next, we tested the potential of lovastatin and VDH in combination to confer protection from EAE. Interestingly, suboptimal doses of these DMAs significantly attenuated acute clinical exacerbations, cellular infiltration, inflammatory response, axonal loss and demyelination in the spinal cord of EAE animals compared with their individual treatment analyzed by using quantitative and qualitative analyses. Altogether, these findings provide initial evidence that lovastatin maintains VDH homeostasis and its synergy with VDH enhances neuroprotection in EAE/MS brain.