A growing body of evidence suggests that social conflict is associated with inflammatory disease onset and exacerbations in multiple sclerosis (MS) patients and in animal models of MS. This review illustrates how animal research can be used to elucidate the biobehavioral mechanisms underlying the adverse health effects of social conflict. The authors review studies indicating that social conflict exacerbates a virally initiated animal model of MS. This research suggests that the deleterious effects of social conflict may be partially mediated by stress-induced increases in pro-inflammatory cytokine levels in the central nervous system. In addition, they provide evidence that the adverse health effects of social conflict can be prevented by blocking the stress-induced increases in cytokine activity. This suggests that interventions designed to prevent or reverse the stress-induced increases in cytokine activity may be able to prevent or reverse some of the negative health effects of social conflict in humans.
Acheson, E.D. (1977). Epidemiology of multiple sclerosis. British MedicalBulletin, 33, 9-14.
2.
Ackerman, K.D., Heyman, R., Rabin, B.S., Anderson, B.P., Houck, P.R., Frank, E., et al. (2002). Stressful life events precede exacerbations of multiple sclerosis. Psychosomatic Medicine, 64, 916-920.
3.
Ackerman, K.D., Stover, A., Heyman, R., Anderson, B.P., Houck, P.R., Frank E., et al. (2003). Relationship of cardiovascular reactivity, stressful life events, and multiple sclerosis disease activity. Brain, Behavior, and Immunity, 17, 141-151.
4.
Adcock, I.M., Ito, K., & Barnes, P.J. (2004). Glucocorticoids: Effects on gene transcription . Proceedings of the American Thoracic Society, 1, 247-254.
5.
Akira, S., Hirano, T., Taga, T., & Kishimoto, T. (1990). Biology of multifunctional cytokines: IL-6 and related molecules (IL1 and TNF). Federation of American Societies for Experimental Biology Journal, 4, 2860-2867.
6.
Aubert, C., Chamorro, M., & Brahic, M. (1987). Identification of Theiler's infected cells in the central nervous system of the mouse during demyelinating disease. Microbial Pathogenesis, 3, 319-326.
7.
Avitsur, R., Stark, J.L., & Sheridan, J.F. (2001). Social stress induces glucocorticoid resistance in subordinate animals. Hormones & Behavior , 39, 247-257.
8.
Backer, J.H. (2000). Stressors, social support, coping, and health dysfunction in individuals with Parkinson's disease. Journal ofGerontological Nursing, 26, 7-16.
9.
Bethin, K.E., Vogt, S.K., & Muglia, L.J. (2000). Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation . Proceedings of the National Academy of Sciences USA, 97, 9317-9322.
10.
Biron, C.A. (1998). Role of early cytokines, including alpha and beta interferons (IFN-α/β), in innate and adaptive immune responses to viral infections. Seminars in Immunology, 10, 383-390.
11.
Blandino, P., Jr., Barnum, C.J., & Deak, T. (2006). The involvement of norepinephrine and microglia in hypothalamic and splenic IL-1beta responses to stress. Journal of Neuroimmunology, 173, 87-95.
12.
Bluthe, R.M., Michaud, B., Poli, V., & Dantzer, R. (2000). Role of IL-6 in cytokine-induced sickness behavior: A study with IL-6 deficient mice. Physiology and Behavior , 70, 367-373.
13.
Borrow, P., Tonks, P., Welsh, C.J.R., & Nash, A.A. (1992). The role of CD8+ T cells in the acute and chronic phases of Theiler's virus-induced disease in mice. Journal of GeneralVirology, 73, 1861-1865.
14.
Brahic, M., Stroop, W.G., & Baringer, J.R. (1981). Theiler's virus persists in glial cells during demyelinating disease. Cell, 26, 123-128.
15.
Campbell, J.C. (2002). Health consequences of intimate partner violence . Lancet, 359, 1331-1336.
16.
Campbell, T., Meagher, M.W., Sieve, A., Scott, B., Storts, R., Welsh, T.H., et al. (2001). The effects of restraint stress on the neuropathogenesis of Theiler's virus infection: I. Acute disease. Brain, Behavior, and Immunity, 15, 235-254.
17.
Campisi, J., & Fleshner, M. (2003). The role of extracellular HSP72 in acute stress-induced potentiation of innate immunity in physically active rats. Journal of Applied Physiology, 94, 43-52.
18.
Carlson, L.E., Speca, M., Patel, K.D., & Goodey, E. (2003). Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate cancer outpatients. Psychosomatic Medicine, 65, 571-581.
19.
Challoner, P.B., Smith, K.T., Parker, J.D., MacLeod, D.L., Coulter, S.N., Rose, T.M., et al. (1995). Plaque-associated expression of human herpes virus 6 in multiple sclerosis. Proceedings of the National Academy of Sciences USA, 92, 7440-7444.
20.
Chancellor-Freeland, C., Zhu, G., Kage, R., Beller, D., Leeman, S., & Black, P. (1995). Substance P and stress-induced changes in macrophages . Annals of the New York Academy of Science, 771, 472-484.
21.
Chida, Y., Sudo, N., & Kubo, C. (2005). Social isolation stress exacerbates autoimmune disease in MRL/LPR mice. Journal of Neuroimmunology, 158, 138-144.
22.
Clatch, R.J., Lipton, H.L. & Miller, S.D. (1987). Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. II. Survey of host immune responses and central nervous system virus titers in inbred mouse strains. Microbial Pathogenesis, 3, 327-337.
23.
Dal Canto, M.C., & Rabinowitz, S.G. (1982). Experimental models of virus-induced demyelination of the central nervous system. Annals of Neurology, 11, 109-127.
24.
Dantzer, R. (2001). Cytokine-induced sickness behavior: Mechanisms and implications. Annals of the New York Academy of Science , 933, 222-234.
25.
DeRijk, R.H., Eskandari, F., & Sternberg, E.M. (2004). Corticosteroid resistance in a subpopulation of multiple sclerosis patients as measured by ex vivo dexamethasone inhibition of LPS induced IL-6 production. Journal of Neuroimmunology , 151, 180-188.
26.
Dethlefs, S., Brahic, M., & Larsson-Sciard, E.L. (1997). An early abundant cytotoxic T-lymphocyte response against Theiler's virus is critical for preventing for viral persistence. Journal ofVirology, 71, 8875-8878.
27.
Dhabhar, F.S., & McEwen, B.S. (1997). Acute stress enhances while chronic stress suppresses immune function in vivo: A role for leukocyte trafficking. Brain, Behavior, and Immunity, 11, 286-306.
28.
Dhabhar, F.S., & McEwen, B.S. (1999). Enhancing versus suppressive effects of stress hormones on skin immune function. Proceedings of the National Academy of Science USA, 96, 1059-1064.
29.
Dobbs, C.M., Vasquez, M., Glaser, R., & Sheridan, J.F. (1993). Mechanisms of stress-induced modulation of viral pathogenesis and immunity. Journal of neuroimmunology, 48, 151-160.
30.
Dowdell, K.C., Gienapp, I.E., Stuckman, S., Wardrop, R.M., & Whitacre, C.C. (1999). Neuroendocrine modulation of chronic relapsing experimental autoimmune encephalomyelitis: A critical role for the hypothalamic-pituitary-adrenal axis. Journal of Neuroimmunology, 100, 243-251.
31.
Earls, F. (1987). Sex differences in psychiatric disorders: Origins and developmental influences. Psychiatric Developments, 5, 1-23.
32.
Eugster, H.P., Frei, K., Kopf, M., Lassmann, H., & Fontana, A. (1998). IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. European Journal of Immunology, 28, 2178-2187.
33.
Fiette, L., Aubert, C., Ulrike, M., Huang, S., Aguet, M., Brahic, M., et al. (1995). Theiler's virus infection of 129Sv mice that lack the interferon α/β or IFN-γ receptors. Journal of ExperimentalMedicine, 181, 2069-2076.
34.
Filippini, G., Munari, L., Incorvaia, B., Ebers, G.C., Polman, C., D'Amico, R., et al. (2003). Interferons in relapsing remitting multiple sclerosis: a systematic review. Lancet, 361(9357), 545-552.
35.
Gielen, R.S., Adams, V., Möbius-Winkler, S., Link, A., Erbs, S., Yu, J., et al. (2003). Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. Journal ofAmerican College of Cardiology, 42, 861-868.
Grant, I., Brown, G.W., Harris, T., McDonald, W.I., Patterson, T., & Trimble, M.R. (1989). Severely threatening events and marked life difficulties preceding onset or exacerbation of multiple sclerosis. Journal ofNeurology, Neurosurgery and Psychiatry, 52, 8-13.
38.
Greenwood, B.N., Kennedy, S., Smith, T.P., Campeau, S., Day, H.E., & Fleshner, M. (2003). Voluntary freewheel running selectively modulates catecholamine content in peripheral tissue and c-Fos expression in the central sympathetic circuit following exposure to uncontrollable stress in rats. Neuroscience, 120, 269-281.
39.
Hermann, G., Beck, M.F., & Sheridan, J.F. (1995). Stress-induced glucocorticoid response modulates mononuclear cell trafficking during an experimental influenza viral infection. Journal of Neuroimmunology, 56, 179-186.
40.
Hernan, M.A., Zhang, S.M., Lipworth, L., Olek, M.J., & Ascherio, A. (2001). Multiple sclerosis and age at infection with common viruses. Epidemiology, 12, 301-306.
41.
Huang, Q.H., Takaki, A., & Arimura, A. (1997). Central noradrenergic system modulates plasma interleukin-6 production by peripheral interleukin-1. Journal of Physiology—Regulatory, Integrative and Comparative Physiology, 273, 731-738.
42.
Johnson, J.D., Campisi, J., Sharkey, C.M., Kennedy, S.L., Nickerson, M., Greenwood, B.N., et al. (2005). Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines. Neuroscience , 135, 1295-1307.
Johnson, R.R., Prentice, T., Bridegam, P., Young, C.R., Steelman, A.J., Welsh, T.H., et al. (2006). Social stress alters the severity and onset of the chronic phase of Theiler's virus infection. Journal of Neuroimmunology, 175, 39-51.
45.
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. Journal of Neuroimmunology, 148, 74-85.
46.
Johnson, R.T. (1994). The virology of demyelinating diseases. Annals of Neurology, 36(Suppl.), S54-60.
47.
Kaminsky, S.G., Nakamura, I., & Cudkowicz, G. (1987). Defective differentiation of natural killer cells in SJL mice. Role of the thymus. Journal of Immunology, 138, 1020-1025.
48.
Kenis, G., & Maes, M. (2002). Effects of antidepressants on the production of cytokines. International Journal of Neuropsychopharmacology , 5, 401-412.
49.
Kurtzke, J.F. (1993). Epidemiologic evidence for multiple sclerosis as an infection. Clinical Microbiology Review, 6, 382-427.
50.
Kurtzke, J.F., & Hyllested, K. (1987). MS epidemiology in Faroe Islands. Review of Neurology, 57, 77-87.
51.
LeMay, L.G., Otterness, I.G., Vander, A.J., & Kluger, M.J. (1990). In vivo evidence that the rise in plasma IL 6 following injection of a fever-inducing dose of LPS is mediated by IL 1 beta . Cytokine, 2, 199-204.
52.
LeMay, L.G., Vander, A.J., & Kluger, M.J. (1990). The effects of psychological stress on plasma interleukin-6 activity in rats. Physiology & Behavior , 47, 957-961.
53.
Levin, L.I., Munger, K.L., Rubertone, M.V., Peck, C.A., Lennette, E.T., Spiegelman, D., et al. (2003). Multiple sclerosis and Epstein-Barr virus. Journal of theAmerican Medical Association, 289, 1533-1536.
54.
Lipton, H.L. (1975). Theiler's virus infection in mice: An unusual biphasic disease process leading to demyelination. Infection andImmunology, 11, 1147-1155.
55.
Maes, M. (2001). Psychological stress and the inflammatory response system. Clinical Science, 101, 193-194.
56.
Maes, M., Bosmans, E., De Jongh, R., Kenis, G., Vandoolaeghe, E., & Neels, H. (1997). Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine, 9, 853-858.
57.
Maier, S.F., & Watkins, L.R., (1998). Cytokines for psychologists: Bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychological Review, 105, 83-107.
58.
Matyszak, M.K. (1998). Inflammation in the CNS: Balance between immunological privilege and immune responses. Progress in Neurobiology, 56, 19-35.
59.
McEwen, B.S., Biron, C.A., Brunson, K.W., Bulloch, K., Chambers, W.H., Dhabhar, F.S., et al. (1997). The role of adrenocorticoids as modulators of immune function in health and disease: Neural, endocrine and immune interactions . Brain Research Review, 23, 79-133.
60.
McGeer, P.L., & McGeer, E.G. (1995). The inflammatory response system of brain: Implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Research Review, 21, 195-218.
61.
Meagher, M.W., Johnson, R.R., Good, E., & Welsh, C.J.R. (2006a). Social stress alters the severity of an animal model of multiple sclerosis. In C. J. Welsh , M. W. Meagher, & E. Sternberg (Eds.), Neural and neuroendocrine mechanisms in host defense and autoimmunity (pp. 216-240). New York: Springer.
62.
Meagher, M.W., Johnson, R.R., Good, E., & Welsh, C.J.R. (2006b). Social stress alters the severity of a virally initiated model of multiple sclerosis. In R. Ader, D. Felton, & N. Cohen (Eds.), Psychoneuroimmunology (4th ed., Vol. 2, pp. 1107-1124). New York: Academic Press.
63.
Meagher, M.W., Johnson, R.R., Young, E.E., Vichaya, E.G., Lunt, S., Harden, E., et al. (in press). IL-6 as a mechanism for the adverse effects of social stress on acute Theiler's virus infection. Brain, Behavior, and Immunity.
64.
Mei-Tal, V., Meyerowitz, S., & Engel, G.L. (1970). The role of psychological process in a somatic disorder: Multiple sclerosis. 1. The emotional setting of illness onset and exacerbation. Psychosomatic Medicine, 32, 67-86.
65.
Mendel, I., Katz, A., Kozak, N., Ben-Nun, A., & Revel, M. (1998). Interleukin-6 functions in autoimmune encephalomyelitis: A study in gene-targeted mice. European Journal ofImmunology , 28, 1727-1737.
66.
Mi, W., Belyavskyi, M., Johnson, R.R., Sieve, A.N., Storts, R., Meagher, M.W., et al. (2004). Alterations in chemokine expression in Theiler's virus infection and restraint stress. Journal of Neuroimmunology, 151, 103-115.
67.
Mi, W., Prentice, T.W., Young, C.R., Johnson, R.R., Sieve, A.N., Meagher, M.W., et al. (2006). Restraint stress decreases virus-induced pro-inflammatory cytokine mRNA expression during acute Theiler's virus infection . Journal of Neuroimmunology, 178, 49-61.
68.
Miller, G.E., Cohen, S., & Ritchey, A.K. (2002). Chronic psychological stress and the regulation of proinflammatory cytokines: A glucocorticoid-resistance model. Health Psychology, 21, 531-541.
69.
Mohr, D.C., Goodkin, D.E., Bacchetti, P., Boudewyn, A.C., Huang, L., Marrietta, P., et al. (2000). Psychological stress and the subsequent appearance of new brain MRI lesions in MS. Neurology, 55, 55-61.
70.
Mohr, D.C., Hart, S.L., Julian, L., Cox, D., & Pelletier, D. (2004). Association between stressful life events and exacerbation in multiple sclerosis: A meta-analysis. British Medical Journal, 328, 731-735.
71.
Mohr, D.C., & Pelletier, D. (2005). A temporal framework for understanding the effects of stressful life events on inflammation in patients with multiple sclerosis . Brain, Behavior, and Immunity, 20, 27-36.
72.
Moore, F.G., & Wolfson, C. (2002). Human herpes virus 6 and multiple sclerosis. Acta Neurologica Scandinavica, 106, 63-83.
73.
Murray, P.D., Pavelko, K.D., Leibowitz, J., Lin, X., & Rodriguez, M. (1998). CD4 (+) and CD8 (+) T cells make discrete contributions to demyelination and neurologic disease in a viral model of multiple sclerosis . Journal of Virology, 72, 7320-7329.
74.
Oleszak, E.L., Chang, J.R., Friedman, H., Katsetos, C.D., & Platsoucas, C.D. (2004). Theiler's virus infection: A model for multiple sclerosis. Clinical Microbiology Reviews , 17, 174-207.
75.
Olson, J.K., Ludovic Croxford, J., & Miller, S.D. (2004). Innate and adaptive immune requirements for induction of autoimmune demyelinating disease by molecular mimicry. Molecular Immunology, 40, 1103-1108.
76.
Padberg, F., Feneberg, W., Schmidt, S., Schwarz, M.J., Korschenhausen, D., Greenberg, B.D., et al. (1999). CSF and serum levels of soluble interleukin-6 receptors (sIL-6R and sgp130), but not of interleukin-6 are altered in multiple sclerosis. Journal of Neuroimmunology, 99, 218-223.
77.
Padgett, D.A., Sheridan, J.F., Dorne, J., Berntson, G.G., Candelora, J., & Glaser, R. (1998). Social stress and the reactivation of latent herpes simplex virus type 1. Proceedings of the National Academy of Science USA, 95, 7231-7235.
78.
Palma, J.P., Kwon, D., Clipstone, N.A., & Kim, B.S. (2003). Infection with Theiler's murine encephalomyelitis virus directly induces proinflammatory cytokines in primary astrocytes via NF-kappaB activation: Potential role for the initiation of demyelinating disease. Journal ofVirology, 77, 6322-6331.
79.
Persoons, J.H., Schornagel, K., Breve, J., Berkenbosch, F., & Kaal, G., (1995). Acute stress affects cytokines and nitric oxide production by alveolar macrophages differently. American Journal of Respiratory Critical Care Medicine, 152, 619-624.
80.
Quan, N., Avitsur, R., Stark, J.L., He, L., Shah, M., Caliguiri, M., et al. (2001). Social stress increases the susceptibility to endotoxic shock. Journal of Neuroimmunology, 115, 36-45.
81.
Rabin, B.S. (2002). Can stress participate in the pathogenesis of autoimmune disease? Journal of AdolescentHealth, 30, 71-75.
82.
Raison, M.C.L., & Miller, A.H. (2003). When not enough is too much: The role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders . American Journal of Psychiatry,160, 1554-1565.
83.
Rodriguez, M., Pavelko, K.D., Njenga, M.K., Logan, W.C., & Wettstein, P.J. (1996). The balance between persistent virus infection and immune cells determines demyelination. Journal ofImmunology, 157, 5699-5709.
84.
Rodriguez, M., & Sriram, S. (1988). Successful therapy of Theiler's virus-induced demyelination (DA strain) with monoclonal anti-Lyt2 antibody. Journal of Immunology, 140, 2950-2955.
85.
Samoilova, E.B., Horton, J.L., Hilliard, B., Liu, T.S., & Chen, Y. (1998). IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: Roles of IL-6 in the activation and differentiation of autoreactive T cells. Journal of Immunology, 161, 6480-6486.
86.
Schonrock, L.M., Gawlowski, G., & Bruck, W. (2000). Interleukin-6 expression in human multiple sclerosis lesions. Neuroscience Letters, 294, 45-48.
87.
Sheridan, J.F., Dobbs, C., Jung, J., Chu, X., Konstantinos, A., Padgett, D.A., et al. (1998). Stress-induced neuroendocrine modulation of viral pathogenesis and immunity. Annals of the New York Academy of Science, 840, 803-808.
88.
Shizuya, K., Komori, T., Fujiwara, R., Miyahara, S., Ohmori, M., & Nomura, J. (1998). The expressions of mRNAs for interleukin-6 (IL-6) and the IL-6 receptor (IL-6R) in the rat hypothalamus and midbrain during restraint stress. Life Science, 62, 2315-2320.
89.
Sieve, A.N., Steelman, A.J., Young, C.R., Storts, R., Welsh, T.H., Welsh, C.J.R., et al. (2004). Chronic restraint stress during early Theiler's virus infection exacerbates the subsequent demyelinating disease in SJL mice . Journal of Neuroimmunology, 155, 103-118.
90.
Sieve, A.N., Steelman, A.J., Young, C.R., Storts, R., Welsh, T.H., Welsh, C.J.R., et al. (2006). Sex-dependent effects of chronic restraint stress during early Theiler's virus infection on the subsequent demyelinating disease in CBA mice. Journal of Neuroimmunology, 177, 46-62.
91.
Simopoulos, A.P. (2002). Omega-3 fatty acids in inflammation and autoimmune diseases. Journal of the American College of Nutrition, 21, 495-505.
92.
Soldan, S.S., & Jacobson, S. (2001). Role of viruses in etiology and pathogenesis of multiple sclerosis. Advances inVirus Research, 56, 517-555.
93.
Sospedra, M., & Martin, R. (2005). Immunology of multiple sclerosis. Annual Review ofImmunology, 23, 683-747.
94.
Stark, J.L., Avitsur, R., Hunzeker, J., Padgett, D.A., & Sheridan, J.F. (2002). Interleukin-6 and the development of social disruption-induced glucocorticoid resistance. Journal of Neuroimmunology, 124, 9-15.
95.
Stark, J.L., Avitsur, R., Padgett, D.A., Campbell, K.A., Beck, F.M., & Sheridan, J.F. (2001). Social stress induces glucocorticoid resistance in macrophages. American Journal of Physiology— Regulatory, Integrative and Comparative Physiology, 280, R1799-1805.
96.
Stefferl, A., Storch, M.K., Linington, C., Stadelmann, C., Lassmann, H., Pohl, T., et al. (2001). Disease progression in chronic relapsing experimental allergic encephalomyelitis is associated with reduced inflammation-driven production of corticosterone. Endocrinology, 142, 3616-3624.
97.
Steptoe, A., Willemsen, G., Owen, N., Flower, L., & Mohamed-Ali, V. (2001). Acute mental stress elicits delayed increases in circulating inflammatory cytokine levels. Clinical Sciences, 101, 185-192.
98.
Takaki, A., Huang, Q.-H., Somogyvari-Vigh, A., & Arimura, A. (1994). Immobilization stress may increase plasma interleukin (IL)-6 via central and peripheral catecholamines. Neuroimmunomodulation , 1, 335-342.
99.
Theil, D.J., Tsunoda, I., Libbey, J.E., Derfuss, T.J., & Fujinami, R.S. (2000). Alterations in cytokine but not chemokine mRNA expression during three distinct Theiler's virus infections . Journal of Neuroimmunology, 104, 22-30.
100.
Theiler, M. (1934). Spontaneous encephalomyelitis of mice-A new virus . Science, 80, 122.
101.
Tilder, F.J., & Schmidt, E.D. (1999). Cross-sensitization between immune and non-immune stressors. A role in depression? Advances in ExperimentalMedical Biology, 461, 179-197.
102.
van Winsen, L.M., Muris, D.F., Polman, C.H., Dijkstra, C.D., van den Berg, T.K., & Uitdehaag, B.M. (2005). Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis. Journal of Clinical Endocrinology and Metabolism, 90, 734-740.
103.
Warren, S., Greenhill, S., & Warren, K.G. (1982). Emotional stress and the development of multiple sclerosis: Case-control evidence of a relationship. Journal of Chronic Disease, 35, 821-831.
104.
Warren, S., Warren, K.G., & Cockerill, R. (1991). Emotional stress and coping in multiple sclerosis (MS) exacerbations. Journal of Psychosomatic Research, 35, 37-47.
105.
Watkins, L.R., & Maier, S.F. (2000). The pain of being sick: Implications of immune-to-brain communication for understanding pain. Annual Review ofPsychology , 51, 29-57.
106.
Watkins, L.R., Maier, S.F., & Goehler, L.E. (1995). Cytokine-to-brain communication: A review & analysis of alternative mechanisms. Life Science, 57, 1011-1026.
107.
Welsh, C.J.R., Blakemore, W.F., Tonks, P., Borrow, P., & Nash, A.A. (1989). Theiler's murine encephalomyelitis virus infection in mice: A persistent viral infection of the central nervous system which induces demyelination. In N. Dimmock (Ed.), Immune responses, virus infection, and disease (pp. 125-147). London: Oxford University Press.
108.
Welsh, C.J.R., Mi, W., Sieve, A.N., Steelman, A.J., Johnson, R.R., Young, C.R., et al. (2006). The effects of restraint stress on the neuropathogenesis of Theiler's virus-induced demyelination, a murine model for multiple sclerosis. In C. J. R. Welsh, M.W. Meagher, & E. Sternberg (Eds.), Neural and neuroendocrine mechanisms in host defense and autoimmunity (pp. 190-225). New York: Springer.
109.
Welsh, C.J.R., Tonks, P., Borrow, P., & Nash, A.A. (1990). Theiler's virus: An experimental model of virus-induced demyelination. Autoimmunity, 6, 105-112.
110.
Welsh, C.J.R., Tonks, P., Nash, A.A., & Blakemore, W.F. (1987). The effect of L3T4 T cell depletion on the pathogenesis of Theiler's murine encephalomyelitis virus infection in CBA mice. Journal of GeneralVirology, 68, 1659-1667.
111.
Whitacre, C.C. (2001). Sex differences in autoimmune disease. Nature Immunology, 2, 777-780.
112.
Whitacre, C.C., Dowdell, K., & Griffin, A.C. (1998). Neuroendocrine influences on experimental autoimmune encephalomyelitis. Annals of the New York Academy of Science , 840, 705-716.
113.
Whitacre, C.C., Reingold, S.C., O'Looney, P.A., & Task Force on Gender. (1999 ). Multiple sclerosis and autoimmunity. Science , 283, 1277-1278.
114.
Wilson, R.S., Evans, D.A., Bienias, J.L., Mendes de Leon, C.F., Schneider, J.A., & Bennett, D.A. (2003). Proneness to psychological distress is associated with risk of Alzheimer's disease. Neurology, 61, 1479-1485.
115.
Zhou, D., Kusnecov, A.W., Shurin, M.R., DePaoli, M., & Rabin, B.S., (1993). Exposure to physical and psychological stressors elevates plasma interleukin 6: Relationship to the activation of hypothalamic-pituitary-adrenal axis. Endocrinology, 133, 2523-2530.
116.
Zhu, G., Chancellor-Freeland, C., Berman, A., Kage, R., Leeman, S., Beller, D., et al. (1995). Endogenous substance P mediates cold-water-stress induced increase in interleukin-6 section from peritoneal macrophages. Journal of Neuroscience, 16, 3745-3752.
