Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA.

Brain Pathol. 1999 Jul;9(3):481-93. Unique Identifier : AIDSLINE MED/99343431
Tsunoda I; Tolley ND; Theil DJ; Whitton JL; Kobayashi H; Fujinami RS; Department of Neurology, University of Utah School of Medicine,; Salt Lake City 84132, USA.

Abstract: Theiler's murine encephalomyelitis virus (TMEV) infection and relapsing-remitting experimental allergic encephalomyelitis (R-EAE) have been used to investigate the viral and autoimmune etiology of multiple sclerosis (MS), a possible Th1-type mediated disease. DNA immunization is a novel vaccination strategy in which few harmful effects have been reported. Bacterial DNA and oligodeoxynucleotides, which contain CpG motifs, have been reported to enhance immunostimulation. Our objectives were two-fold: first, to ascertain whether plasmid DNA, pCMV, which is widely used as a vector in DNA immunization studies, could exert immunostimulation in vitro; and second, to test if pCMV injection could modulate animal models for MS in vivo. We demonstrated that this bacterially derived DNA could induce interleukin (IL)-12, interferon (IFN)gamma, (Th1-promoting cytokines), and IL-6 production as well as activate NK cells. Following pCMV injections, SJL/J mice were infected with TMEV or challenged with encephalitogenic myelin proteolipid protein (PLP) peptides. pCMV injection exacerbated TMEV-induced demyelinating disease in a dose-dependent manner. Exacerbation of the disease did not correlate with the number of TMEV-antigen positive cells but did with an increase in anti-TMEV antibody. pCMV injection also enhanced R-EAE with increased IFNgamma and IL-6 responses. These results caution the use of DNA vaccination in MS patients and other possible Th1-mediated diseases.

Keywords: JOURNAL ARTICLE Animal Antibodies, Viral/BLOOD CpG Islands/IMMUNOLOGY Cytokines/BIOSYNTHESIS Cytomegalovirus/IMMUNOLOGY Disease Models, Animal Dose-Response Relationship, Drug DNA, Bacterial/*ADVERSE EFFECTS/IMMUNOLOGY Encephalomyelitis, Allergic/GENETICS/IMMUNOLOGY/PATHOLOGY Female Genetic Vectors/ADVERSE EFFECTS/IMMUNOLOGY IgG/BLOOD Killer Cells, Natural/IMMUNOLOGY Mice Mice, Inbred Strains Multiple Sclerosis/*IMMUNOLOGY/*MICROBIOLOGY/PATHOLOGY Myelin Proteolipid Protein/IMMUNOLOGY Spinal Cord/PATHOLOGY Support, U.S. Gov't, P.H.S. Theiler Murine Encephalomyelitis Virus/IMMUNOLOGY Th1 Cells/IMMUNOLOGY Vaccines, DNA/ADVERSE EFFECTS/IMMUNOLOGY
991230
A99C1022

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