Immunomodulatory synergy by combining atorvastatin and rapamycin in the treatment of experimental autoimmune encephalomyelitis (EAE)

Combination therapies are gaining momentum over monotherapies in the treatment of multiple sclerosis (MS). Suboptimal doses of atorvastatin and rapamycin prevented or reversed clinical and histologic experimental autoimmune encephalomyelitis (EAE). Secretion of proinflammatory Th1 and Th17 cytokines was reduced and Th2 and Treg cytokine secretion was increased in mice. Combination therapy promoted induction of Treg cells and attenuated the infiltration of inflammatory IL-17 cells in EAE. It appeared that rapamycin-reactivated ERK was blunted by addition of atorvastatin. Our results demonstrate that agents with different mechanisms of immune modulation can combine synergistically in treating CNS autoimmunity.