title: 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.
authors.affiliation: Department of Psychology, College of Liberal Arts, Texas A&M University, College Station, TX 77843-4235, USA. m-meagher@tamu.edu
authors.forename: Mary W
authors.initials: MW
authors.lastname: Meagher
authors.forename: Robin R
authors.initials: RR
authors.lastname: Johnson
authors.forename: Erin E
authors.initials: EE
authors.lastname: Young
authors.forename: Elisabeth G
authors.initials: EG
authors.lastname: Vichaya
authors.forename: Shannon
authors.initials: S
authors.lastname: Lunt
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hardin
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Connor
authors.forename: C Jane R
authors.initials: CJ
authors.lastname: Welsh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000276:immunology / Q000821:virology; D018188:Cardiovirus Infections / Q000150:complications / Q000276:immunology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005938:Glucocorticoids / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology / Q000523:psychology; D015213:Neuroimmunomodulation; D012803:Sick Role; D012931:Social Environment; D013116:Spinal Cord / Q000276:immunology / Q000821:virology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology* / Q000821:virology; D017945:Theilovirus / Q000276:immunology*
chemical_list: D005938:Glucocorticoids; D015850:Interleukin-6