Interleukin-6 as a mechanism for the adverse effects of social stress on acute Theiler’s virus infection

Abstract

Prior exposure to social disruption stress (SDR) exacerbates both the acute and chronic phase of Theiler's murine encephalomyelitis virus infection (TMEV; [Johnson, R.R., Storts, R., Welsh, T.H., Jr., Welsh, C.J., Meagher, M.W., 2004. Social stress alters the severity of acute Theiler's virus infection. J. Neuroimmunol. 148, 74--85; Johnson, R.R., Prentice, T.W., Bridegam, P., Young, C.R., Steelman, A.J., Welsh, T.H., Welsh, C.J.R., Meagher, M.W., 2006. Social stress alters the severity and onset of the chronic phase of Theiler's virus infection. J. Neuroimmunol. 175, 39--51]). However, the neuroimmune mechanism(s) mediating this effect have not been determined. The present study examined whether stress-induced increases in the proinflammatory cytokine interleukin-6 (IL-6) contributes to the adverse effects of SDR on acute TMEV infection. Experiment 1 demonstrated that SDR increases central and peripheral levels of IL-6 and that this effect is reversed by intracerebral ventricular infusion of neutralizing antibody to IL-6 prior to each of six SDR sessions. Although SDR reduced the sensitivity of spleen cells to the anti-inflammatory effects of corticosterone, the neutralizing antibody to IL-6 did not alter this effect. To investigate whether stress-induced increases in IL-6 contribute to the exacerbation of acute TMEV infection, Experiment 2 examined whether intracerebral administration of neutralizing antibody to IL-6 during SDR would prevent the subsequent exacerbation of acute TMEV infection. Experiment 3 then replaced the social stress with intracerebral infusion of IL-6 to assess sufficiency. As expected, prior exposure to SDR subsequently increased infection-related sickness behaviors, motor impairment, CNS viral titers, and CNS inflammation. These deleterious effects of SDR were either prevented or significantly attenuated by intracerebral infusion of neutralizing antibody to IL-6 during the stress exposure period. However, infusion of IL-6 alone did not mimic the adverse effects of SDR. We conclude that IL-6 is necessary but not sufficient to exacerbate acute TMEV infection.

Effect of transport stress on peripheral blood lymphocyte subsets and Th cytokines in pigs

“…2-3, 177-190 of leukocyte number and decrease of lymphocyte number in the peripheral blood of gilt (Dalin et al, 1993). The function of lymphocytes, and the production of cytokines, can be influenced by a variety of stressors (Meagher et al, 2007). T lymphocytes play a variety of important roles in immune regulation, inflammation, and protective immune response throu responses of lymphocyte subsets (Wilhelm et al, 2009).…”

Neuroimmune mechanisms of depression

“…Intracranial infusions of IL-6 91 or administration of IL-1b 92, 93 into the hippocampus increase depression associated behavior and reduces neurogenesis, whereas infusion of IL-1b 93 and IL-6 91 antibodies, or genetic deletion of IL-6 94 , blocks the depressive-like effects induced by CMS. Cytokines can act on serotonin neurons through the kynurenine pathway and tryptophan catabolites 95, 96 as well as directly on glutamatergic neurons in the frontal cortex 97 and hippocampus 98 to alter synaptic plasticity.…”

Social isolation alters neuroinflammatory response to stroke

“…The neutralizing antibody to IL-6 (10 ng in 2 L vehicle) (zcomR&D Systems) or vehicle, 2 L aCSF, was infused 1 h before MCAO surgery. This dose has been used successfully to neutralize IL-6 signaling in mice (48). According to the manufacturer, this dose is within range of the 50% neutralization dose determined in the presence of 0.25 ng/mL rmIL-6 (R&D Systems anti-mouse IL-6 Ab, AF-406-NA).…”