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

Brain Pathol. 1999 Jul;9(3):481-93. doi: 10.1111/j.1750-3639.1999.tb00537.x.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • CpG Islands / immunology
  • Cytokines / biosynthesis
  • Cytomegalovirus / immunology
  • DNA, Bacterial / adverse effects*
  • DNA, Bacterial / immunology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Genetic Vectors / adverse effects
  • Genetic Vectors / immunology
  • Immunoglobulin G / blood
  • Killer Cells, Natural / immunology
  • Mice
  • Mice, Inbred Strains
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / microbiology*
  • Multiple Sclerosis / pathology
  • Myelin Proteolipid Protein / immunology
  • Spinal Cord / pathology
  • Th1 Cells / immunology
  • Theilovirus / immunology
  • Vaccines, DNA / adverse effects
  • Vaccines, DNA / immunology

Substances

  • Antibodies, Viral
  • Cytokines
  • DNA, Bacterial
  • Immunoglobulin G
  • Myelin Proteolipid Protein
  • Vaccines, DNA