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Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA.
- Source :
-
Brain pathology (Zurich, Switzerland) [Brain Pathol] 1999 Jul; Vol. 9 (3), pp. 481-93. - Publication Year :
- 1999
-
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.
- Subjects :
- Animals
Antibodies, Viral blood
CpG Islands immunology
Cytokines biosynthesis
Cytomegalovirus immunology
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 pathology
Myelin Proteolipid Protein immunology
Spinal Cord pathology
Th1 Cells immunology
Theilovirus immunology
Vaccines, DNA adverse effects
Vaccines, DNA immunology
DNA, Bacterial adverse effects
Multiple Sclerosis immunology
Multiple Sclerosis microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1015-6305
- Volume :
- 9
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Brain pathology (Zurich, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 10416988
- Full Text :
- https://doi.org/10.1111/j.1750-3639.1999.tb00537.x