title: Cuprizone and piperonyl butoxide, proposed inhibitors of T-cell function, attenuate experimental allergic encephalomyelitis in SJL mice.
abstract: Multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), are autoimmune demyelinating diseases with autoreactive T-cells acting as important mediators of pathogenesis. Cuprizone, a copper chelator, and piperonyl butoxide (PBO), a pesticide synergist, are implicated to inhibit T-cell activation and function. The purpose of this study was to assess whether either of these agents would suppress PLP-peptide-induced EAE in the SJL mouse. Indeed, treatment with cuprizone beginning 1 week prior to disease induction, and PBO administration from days 1 to 9 of EAE, significantly attenuated EAE clinical severity. Furthermore, both agents decreased blood CD4+/CD8+ ratios, and reduced signs of chronic graft vs. host disease (GVHD) indicating attenuation of an immune T-cell response. These results suggest that cuprizone and PBO suppress EAE and use of these agents will provide insights into the mechanisms of T-cell mediated diseases.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Emerson
authors.forename: S
authors.initials: S
authors.lastname: Biswas
authors.forename: S M
authors.initials: SM
authors.lastname: LeVine
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D002614:Chelating Agents / Q000494:pharmacology*; D002908:Chronic Disease; D003471:Cuprizone / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D010574:Pesticide Synergists / Q000494:pharmacology*; D010882:Piperonyl Butoxide / Q000494:pharmacology*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D002614:Chelating Agents; D010574:Pesticide Synergists; D003471:Cuprizone; D010882:Piperonyl Butoxide