Lithium prevents and ameliorates experimental autoimmune encephalomyelitis

Patrizia De Sarno, Robert C. Axtell, Chander Raman, Kevin A. Roth, Dario R. Alessi, Richard S Jope

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Experimental autoimmune encephalomyelitis (EAE) models, in animals, many characteristics of multiple sclerosis, for which there is no adequate therapy. We investigated whether lithium, an inhibitor of glycogen synthase kinase-3 (GSK3), can ameliorate EAE in mice. Pretreatment with lithium markedly suppressed the clinical symptoms of EAE induced in mice by myclin oligodendrocyte glycoprotein peptide (MOG 35-55) immunization and greatly reduced demyelination, microglia activation, and leukocyte infiltration in the spinal cord. Lithium administered postimmunization, after disease onset, reduced disease severity and facilitated partial recovery. Conversely, in knock-in mice expressing constitutively active GSK3, EAE developed more rapidly and was more severe. In vivo lithium therapy suppressed MOG 35-55- reactive effector T cell differentiation, greatly reducing in vitro MOG 35-55stimulated proliferation of mononuclear cells from draining lymph nodes and spleens, and MOG 35-55-induced IFN-γ, IL-6, and IL-17 production by splenocytes isolated from MOG 35-55-immunized mice. In relapsing/remitting EAE induced with proteolipid protein peptide 139-151, lithium administered after the first clinical episode maintained long-term (90 days after immunization) protection, and after lithium withdrawal the disease rapidly relapsed. These results demonstrate that lithium suppresses EAE and identify GSK3 as a new target for inhibition that may be useful for therapeutic intervention of multiple sclerosis and other autoimmune and inflammatory diseases afflicting the CNS.

Original languageEnglish
Pages (from-to)338-345
Number of pages8
JournalJournal of Immunology
Volume181
Issue number1
StatePublished - Dec 1 2008
Externally publishedYes

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Autoimmune Experimental Encephalomyelitis
Lithium
Glycogen Synthase Kinase 3
Multiple Sclerosis
Immunization
Myelin-Oligodendrocyte Glycoprotein
Peptides
Interleukin-17
Oligodendroglia
Microglia
Demyelinating Diseases
Autoimmune Diseases
Cell Differentiation
Interleukin-6
Spinal Cord
Leukocytes
Therapeutics
Spleen
Animal Models
Lymph Nodes

ASJC Scopus subject areas

  • Immunology

Cite this

De Sarno, P., Axtell, R. C., Raman, C., Roth, K. A., Alessi, D. R., & Jope, R. S. (2008). Lithium prevents and ameliorates experimental autoimmune encephalomyelitis. Journal of Immunology, 181(1), 338-345.

Lithium prevents and ameliorates experimental autoimmune encephalomyelitis. / De Sarno, Patrizia; Axtell, Robert C.; Raman, Chander; Roth, Kevin A.; Alessi, Dario R.; Jope, Richard S.

In: Journal of Immunology, Vol. 181, No. 1, 01.12.2008, p. 338-345.

Research output: Contribution to journalArticle

De Sarno, P, Axtell, RC, Raman, C, Roth, KA, Alessi, DR & Jope, RS 2008, 'Lithium prevents and ameliorates experimental autoimmune encephalomyelitis', Journal of Immunology, vol. 181, no. 1, pp. 338-345.
De Sarno P, Axtell RC, Raman C, Roth KA, Alessi DR, Jope RS. Lithium prevents and ameliorates experimental autoimmune encephalomyelitis. Journal of Immunology. 2008 Dec 1;181(1):338-345.
De Sarno, Patrizia ; Axtell, Robert C. ; Raman, Chander ; Roth, Kevin A. ; Alessi, Dario R. ; Jope, Richard S. / Lithium prevents and ameliorates experimental autoimmune encephalomyelitis. In: Journal of Immunology. 2008 ; Vol. 181, No. 1. pp. 338-345.
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