Methylprednisolone induces reversible clinical and pathological remission and loss of lymphocyte reactivity to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of human multiple sclerosis (MS). EAE, induced by immunisation with myelin-associated autoantigens, is characterised by an inflammatory infiltrate in the central nervous system (CNS) associated with axonal degeneration, demyelination and damage. We have recently shown in an experimental mouse model of autoimmune gastritis that methylprednisolone treatment induces a reversible remission of gastritis with regeneration of the gastric mucosa. Here, we examined the effect of oral methylprednisolone on the mouse EAE model of human MS induced by immunisation with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)). We examined the clinical scores, CNS pathology and lymphocyte reactivity to MOG(35-55) following treatment and withdrawal of the steroid. Methylprednisolone remitted the clinical signs of EAE and the inflammatory infiltrate in the CNS, accompanied by loss of lymphocyte reactivity to MOG(35-55) peptide. Methylprednisolone withdrawal initiated relapse of the clinical features, a return of the CNS inflammatory infiltrate and lymphocyte reactivity to MOG(35-55) peptide. This is the first study to show that methylprednisolone induced a reversible remission in the clinical and pathological features of EAE in mice accompanied by loss of lymphocyte reactivity to the encephalitogen. This model will be useful for studies directed at a better understanding of mechanisms associated with steroid-induced disease remission, relapse and remyelination and also as an essential adjunct to an overall curative strategy.
Department of Medicine, Centre for Inflammatory Diseases, Monash University, Clayton, Vic., Australia.
James
J
Chan
Ee Jun
EJ
Ban
Keng Hao
KH
Chun
Shunhe
S
Wang
Jonathan
J
McQualter
Claude
C
Bernard
Ban-Hock
BH
Toh
Frank
F
Alderuccio
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D008213:Lymphocyte Activation; D008775:Methylprednisolone / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D012074:Remission Induction; D013116:Spinal Cord / Q000473:pathology
D000893:Anti-Inflammatory Agents; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D008775:Methylprednisolone