title: Oral zinc aspartate treats experimental autoimmune encephalomyelitis.
abstract: The essential trace element zinc plays a critical role in the regulation of immune homeostasis. Zinc deficiency or excess can cause severe impairment of the immune response, which points to the importance of the physiological and dietary control of zinc levels for a functioning immune system. We previously reported that injection of zinc aspartate suppresses experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), as well as effector T cell functions in vitro. Among the preferred characteristics of novel therapeutics for the treatment of autoimmune diseases such as MS are oral availability and a tolerable effective dose to minimize side effects. In this study, we investigated whether oral administration of zinc aspartate, an approved drug to treat zinc deficiency in humans, is effective in controlling EAE at clinically approved doses. We show that oral administration of 6 µg/day [0.3 mg/kg body weight (BW)] or 12 µg/day [0.6 mg/kg BW] of zinc aspartate reduces clinical and histopathological signs during the relapsing remitting phase of the disease in SJL mice. The clinical effect in mice was accompanied by suppression of IFN-γ, TNF-α, GM-CSF and IL-5 production in stimulated human T cells and mouse splenocytes in a dose-dependent manner. Furthermore, a large array of proinflammatory cytokines was modulated by zinc aspartate exposure in vitro. These data suggest that administration of oral zinc aspartate may have beneficial effects on autoimmune diseases like MS.
authors.affiliation: Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schubert
authors.forename: Karina
authors.initials: K
authors.lastname: Guttek
authors.forename: Kurt
authors.initials: K
authors.lastname: Grüngreiff
authors.forename: Anja
authors.initials: A
authors.lastname: Thielitz
authors.forename: Frank
authors.initials: F
authors.lastname: Bühling
authors.forename: Annegret
authors.initials: A
authors.lastname: Reinhold
authors.forename: Stefan
authors.initials: S
authors.lastname: Brocke
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhold
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D056831:Coordination Complexes / Q000494:pharmacology / Q000627:therapeutic use*; D004306:Dose-Response Relationship, Immunologic; D004353:Drug Evaluation, Preclinical; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015032:Zinc / Q000097:blood
chemical_list: D056831:Coordination Complexes; D008222:Lymphokines; D001224:Aspartic Acid; D015032:Zinc