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.
Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.
Zhenfei
Z
Li
Liping
L
Chen
Xiaoli
X
Niu
Jia
J
Liu
Man
M
Ping
Ru
R
Li
Xiaohua
X
Xie
Li
L
Guo
D000818:Animals; D000069059:Atorvastatin; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006538:Heptanoic Acids / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D011758:Pyrroles / Q000008:administration & dosage*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000008:administration & dosage*; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D006538:Heptanoic Acids; D007155:Immunologic Factors; D011758:Pyrroles; D000069059:Atorvastatin; D048049:Extracellular Signal-Regulated MAP Kinases; D020123:Sirolimus