Social Stress Sensitizes Theiler's Virus-induced Cytokine Expresssion



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Our laboratory has previously shown that exposure to social disruption (SDR) the week prior to Theiler?s murine encephalomyelitis virus (TMEV) infection exacerbates disease course, resulting in increased infection-related sickness behaviors, motor impairment, CNS viral titers, and CNS inflammation. These adverse effects of SDR were prevented by ICV infusion of a neutralizing antibody to IL-6 during the stress exposure period. These findings suggest that stress-induced increases in IL-6 are necessary to exacerbate acute TMEV infection, but the exact mechanism remains unknown. This thesis tested the hypotheses that SDR up-regulates central cytokine expression, exacerbates TMEV infection through cross-sensitization of virus-induced cytokine expression, and that social rank modulates the effect of SDR. In Experiment 1, Balb/cJ mice underwent the 0, 1, or 6 SDR sessions and were then sacrificed 0, 2, or 12 hours post SDR. Experiment 2 subjects received ICV infusions of either IL-6 neutralizing antibody or its vehicle before each of six 2 h SDR sessions or the control condition, the week prior to infection. In Experiment 3 mice were tested for pre-existing social rank prior to SDR and infection. Results indicate that (1) SDR increases virus-induced IL-6, IL-1B, and CD11b mRNA expression in brain,that these SDR-induced increases and acute TMEV exacerbation are prevented by ICV infusion of the IL-6 neutralizing antibody during the stress exposure period, and that (2) social rank does not modulate affects of SDR but baseline anxiety does. These findings suggest that SDR exacerbates acute TMEV infection through cross-sensitization of virus-induced cytokine expression and that baseline anxiety is a significant modulator of SDR.