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

Theiler's murine encephalomyelitis virus (TMEV) infection and relapsing-rem itting experimental allergic encephalomyelitis (R-EAE) have been used to in vestigate the viral and autoimmune etiology of multiple sclerosis (MS), a p ossible 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 enh ance immunostimulation. Our objectives were two-fold: first, to ascertain w hether plasmid DNA, pCMV, which is widely used as a vector in DNA immunizat ion studies, could exert immunostimulation in vitro; and second, to test if pCMV injection could modulate animal models for MS in vivo. We demonstrate d that this bacterially derived DNA could induce interleukin (IL)-12, inter feron (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 IFN gamma , and IL-6 responses. These results caution the use of DNA vaccination in M S patients and other possible Th1-mediated diseases.