Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone

Frontiers in Neurology

Volumn 4 MAR, Issue , 2013, Pages

  Ross, Amy Perrin ^a   Ben Zacharia, Aliza ^b   Harris, Colleen ^c   Smrtka, Jennifer ^d  

^a LOYOLA UNIVERSITY CHICAGO   (United States)

^b MOUNT SINAI MEDICAL CENTER   (United States)

^c UNIVERSITY OF CALGARY   (Canada)

^d Ft Lauderdale MS Center   (United States)

Author keywords

Adrenocorticotropic hormone; Anti inflammatory; Corticosteroids; Immune modulation; Melanocortins; MS relapses; Multiple sclerosis

Indexed keywords

ALPHA INTERMEDIN; BETA INTERMEDIN; CORTICOSTEROID; CORTICOTROPIN; CXCL1 CHEMOKINE; CXCL2 CHEMOKINE; GADOLINIUM; GAMMA INTERFERON; GAMMA INTERMEDIN; GLATIRAMER; HYDROCORTISONE; IMMUNOGLOBULIN; MELANOCORTIN; MELANOCORTIN RECEPTOR; METHYLPREDNISOLONE; MONOCYTE CHEMOTACTIC PROTEIN 1; NEUROTRANSMITTER; PREDNISONE; RANTES; TUMOR NECROSIS FACTOR ALPHA;

ADRENERGIC SYSTEM; ANTIINFLAMMATORY ACTIVITY; ARTICLE; AUTOIMMUNE DISEASE; AVASCULAR NECROSIS; AXONAL INJURY; B LYMPHOCYTE; BEHAVIOR CHANGE; BLOOD BRAIN BARRIER; CATARACT; CD4+ T LYMPHOCYTE; CELL ACTIVATION; CELL INFILTRATION; CELL MIGRATION; CENTRAL NERVOUS SYSTEM; CLINICAL FEATURE; CLINICAL PRACTICE; COGNITIVE DEFECT; CUSHINGOID SYNDROME; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DEGENERATIVE DISEASE; DEMYELINATION; DISEASE ACTIVITY; DISEASE ASSOCIATION; DISEASE EXACERBATION; DISEASE SEVERITY; DOSE RESPONSE; DRUG CONTRAINDICATION; DRUG EFFICACY; DRUG MEGADOSE; DRUG PULSE THERAPY; EDEMA; EUPHORIA; FATIGUE; FEEDBACK SYSTEM; FLUID RETENTION; GASTROINTESTINAL SYMPTOM; GLAUCOMA; GLUCOSE TOLERANCE; HEALTH CARE QUALITY; HELPER CELL; HORMONE ACTION; HUMAN; HYDROCORTISONE RELEASE; HYPERGLYCEMIA; HYPERNATREMIA; HYPERTENSION; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; INCREASED APPETITE; INFECTION; INFLAMMATION; INFLAMMATORY CELL; INSOMNIA; LONG TERM CARE; MACROPHAGE; MEDIATOR; MEDIATOR RELEASE; MEMBRANE PERMEABILITY; MICROGLIA; MOOD CHANGE; MULTIPLE SCLEROSIS; NERVE DEGENERATION; NERVE ENDING; NEUROENDOCRINE SYSTEM; NONHUMAN; OSTEOPOROSIS; PATHOPHYSIOLOGY; PHYSICAL DISABILITY; PLASMAPHERESIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN SYNTHESIS; PROTEIN SYNTHESIS INHIBITION; PSYCHOSIS; REGULATORY T LYMPHOCYTE; RELAPSE; REMYELINIZATION; SIDE EFFECT; STEROIDOGENESIS; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TASTE DISORDER; TREATMENT DURATION; TREATMENT OUTCOME; WALLERIAN DEGENERATION; WEIGHT GAIN;

EID: 84878797304     PISSN: None     EISSN: 16642295     Source Type: Journal    
DOI: 10.3389/fneur.2013.00021     Document Type: Article

References (159)

1. Adan, R. A., and Gispen, W. H. (1997). Brain melanocortin receptors: from cloning to function. Peptides 18, 1279-1287.
2. Airla, N., Luomala, M., Elovaara, I., Kettunen, E., Knuutila, S., and Lehtimäki, T. (2004). Suppression of immune system genes by methylprednisolone in exacerbations of multiple sclerosis. Preliminary results. J. Neurol. 251, 1215-1219.
3. Andersen, G. N., Hägglund, M., Nagaeva, O., Frängsmyr, L., Petrovska, R., Mincheva-Nilsson, L., et al. (2005). Quantitative measurement of the levels of melanocortin receptor subtype 1, 2, 3, and 5 and pro-opio-melanocortin peptide gene expression in subsets of human peripheral blood leucocytes. Scand. J. Immunol. 61, 279-284.
4. Awad, M. A., and Stuve, O. (2010). Immunopathogenesis of multiple sclerosis: new insights and therapeutic implications. Continuum (Minneap. Minn.) 16, 166-180.
5. Baldwin, A. S. Jr. (1996). The NF-?B and I?B proteins: new discoveries and insights. Annu. Rev. Immunol. 14, 649-683.
6. Baram, T. Z., Mitchell, W. G., Tournay, A., Snead, O. C., Hanson, R. A., and Horton, E. J. (1996). High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics 97, 375-379.
7. Beg, A. A., Finco, T. S., Nantermet, P. V., and Baldwin, A. S. Jr. (1993). Tumor necrosis factor and interlukin-1 lead to phosphorylation and loss of I?Ba: a mechanism for NF-?B activation. Mol. Cell. Biol. 13, 3301-3310.
8. Berer, K., Wekerle, H., and Krishnamoorthy, G. (2011). B cells in spontaneous autoimmune diseases of the central nervous system. Mol. Immunol. 48, 1332-1337.
9. Bhardwaj, R. S., Schwarz, A., Becher, E., Mahnke, K., Aragane, Y., Schwarz, T., et al. (1996). Pro-opiomelanocortin-derived peptides induce IL-10 production in human monocytes. J. Immunol. 156, 2517-2521.
10. Bitsch, A., Schuchardt, J., Bunkowski, S., Kuhlmann, T., and Brück, W. (2000). Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 123(Pt 6), 1174-1183.
11. Bjartmar, C., Kinkel, R. P., Kidd, G., Rudick, R. A., and Trapp, B. D. (2001). Axonal loss in normal-appearing white matter in a patient with acute MS. Neurology 57, 1248-1252.
12. Böhm, M., Eickelmann, M., Li, Z., Schneider, S. W., Oji, V., Diederichs, S., et al. (2005). Detection of functionally active melanocortin receptors and evidence for an immunoregulatory activity of alpha-melanocyte-stimulating hormone in human dermal papilla cells. Endocrinology 146, 4635-4646.
13. Böhm, M., Schulte, U., Kalden, H., and Luger, T. A. (1999). Alpha-melanocyte-stimulating hormone modulates activation of NF-kappa B and AP-1 and secretion of interleukin-8 in human dermal fibroblasts. Ann. N. Y. Acad. Sci. 885, 277-286.
14. Boppana, S., Huang, H., Ito, K., and Dhib-Jalbut, S. (2011). Immunologic aspects of multiple sclerosis. Mt. Sinai J. Med. 78, 207-220.
15. Breij, E. C., Brink, B. P., Veerhuis, R., van den Berg, C., Vloet, R., Yan, R., et al. (2008). Homogeneity of active demyelinating lesions in established multiple sclerosis. Ann. Neurol. 63, 16-25.
16. Brod, S. A., and Hood, Z. M. (2011). Ingested (oral) ACTH inhibits EAE. J. Neuroimmunol. 232, 131-135.
17. Bruck, W. (2005a). The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage. J. Neurol. 252(Suppl. 5), v3-v9.
18. Bruck, W. (2005b). Inflammatory demyelination is not central to the pathogenesis of multiple sclerosis. J. Neurol. 252(Suppl. 5), v10-v15.
19. Brzoska, T., Luger, T. A., Maaser, C., Abels, C., and Böhm, M. (2008). Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocr. Rev. 29, 581-602.
20. Burton, J. M., O'Connor, P. W., Hohol, M., and Beyene, J. (2009). Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database Syst. Rev. 3, CD006921.
21. Carson, M. J. (2002). Microglia as liaisons between the immune and central nervous systems: functional implications for multiple sclerosis. Glia 40, 218-231.
22. Carson, M. J., Thrash, J. C., and Walter, B. (2006). The cellular response in neuroinflammation: the role of leukocytes, microglia and astrocytes in neuronal death and survival. Clin. Neurosci. Res. 6, 237-245.
23. Casanova, B., Martínez-Bisbal, M. C., Valero, C., Celda, B., Martí-Bonmatí, L., Pascual, A., et al. (2003). Evidence of Wallerian degeneration in normal appearing white matter in the early stages of relapsing-remitting multiple sclerosis: a HMRS study. J. Neurol. 250, 22-28.
24. Catania, A. (2008). Neuroprotective actions of melanocortins: a therapeutic opportunity. Trends Neurosci. 31, 353-360.
25. Catania, A., Garofalo, L., Cutuli, M., Gringeri, A., Santagostino, E., and Lipton, J. M. (1998). Melanocortin peptides inhibit production of proinflammatory cytokines in blood of HIV-infected patients. Peptides 19, 1099-1104.
26. Catania, A., Gatti, S., Colombo, G., and Lipton, J. M. (2004). Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol. Rev. 56, 1-29.
27. Catania, A., Lonati, C., Sordi, A., Carlin, A., Leonardi, P., and Gatti, S. (2010). The melanocortin system in control of inflammation. ScientificWorldJournal 10, 1840-1853.
28. Chandran, S., Hunt, D., Joannides, A., Zhao, C., Compston, A., and Franklin, R. J. (2008). Myelin repair: the role of stem and precursor cells in multiple sclerosis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 363, 171-183.
29. Chang, J. Y., and Liu, L. Z. (2000). Catecholamines inhibit microglial nitric oxide production. Brain Res. Bull. 52, 525-530.
30. Chelmicka-Schorr, E., Checinski, M., and Arnason, B. G. (1988). Chemical sympathectomy augments the severity of experimental allergic encephalomyelitis. J. Neuroimmunol. 17, 347-350.
31. Chen, W., Kelly, M. A., Opitz-Araya, X., Thomas, R. E., Low, M. J., and Cone, R. D. (1997). Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell 91, 789-798.
32. Chhajlani, V. (1996). Distribution of cDNA for melanocortin receptor subtypes in human tissues. Biochem. Mol. Biol. Int. 38, 73-80.
33. Chiao, H., Foster, S., Thomas, R., Lipton, J., and Star, R. A. (1996). Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation. J. Clin. Invest. 97, 2038-2044.
34. Chrousos, G. P. (1995). The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N. Engl. J. Med. 332, 1351-1362.
35. Compston, A., and Coles, A. (2008). Multiple sclerosis. Lancet 372, 1502-1517.
36. Confavreux, C., Vukusic, S., Moreau, T., and Adeleine, P. (2000). Relapses and progression of disability in multiple sclerosis. N. Engl. J. Med. 343, 1430-1438.
37. Cooper, A., Robinson, S. J., Pickard, C., Jackson, C. L., Friedmann, P. S., and Healy, E. (2005). Alpha-melanocyte-stimulating hormone suppresses antigen-induced lymphocyte proliferation in humans independently of melanocortin 1 receptor gene status. J. Immunol. 175, 4806-4813.
38. Correale, J., and Villa, A. (2007). The blood-brain-barrier in multiple sclerosis: functional roles and therapeutic targeting. Autoimmunity 40, 148-160.
39. Correale, J., and Villa, A. (2010). Role of CD8+ CD25+ Foxp3+ regulatory T cells in multiple sclerosis. Ann. Neurol. 67, 625-638.
40. Cortese, I., Chaudhry, V., So, Y. T., Cantor, F., Cornblath, D. R., and Rae-Grant, A. (2011). Evidence-based guideline update: plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 76, 294-300.
41. Costantino, C. M., Baecher-Allan, C., and Hafler, D. A. (2008). Multiple sclerosis and regulatory T cells. J. Clin. Immunol. 28, 697-706.
42. De Stefano, N., Narayanan, S., Francis, S. J., Smith, S., Mortilla, M., Tartaglia, M. C., et al. (2002). Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability. Arch. Neurol. 59, 1565-1571.
43. de Wied, D., and Jolles, J. (1982). Neuropeptides derived from pro-opiocortin: behavioral, physiological, and neurochemical effects. Physiol. Rev. 62, 976-1059.
44. Delgado, R., Carlin, A., Airaghi, L., Demitri, M. T., Meda, L., Galimberti, D., et al. (1998). Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia. J. Leukoc. Biol. 63, 740-745.
45. DeLuca, G. C., Williams, K., Evangelou, N., Ebers, G. C., and Esiri, M. M. (2006). The contribution of demyelination to axonal loss in multiple sclerosis. Brain 129, 1507-1516.
46. Duddy, M., Niino, M., Adatia, F., Hebert, S., Freedman, M., Atkins, H., et al. (2007). Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J. Immunol. 178, 6092-6099.
47. Elovaara, I., Apostolski, S., van Doorn, P., Gilhus, N. E., Hietaharju, A., Honkaniemi, J., et al. (2008). EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. Eur. J. Neurol. 15, 893-908.
48. Elovaara, I., Kuusisto, H., Paalavuo, R., Särkijärvi, S., Lehtimäki, T., Huhtala, H., et al. (2006). Effect of high-dose methylprednisolone treatment on CCR5 expression on blood cells in MS exacerbation. Acta Neurol. Scand. 113, 163-166.
49. Färber, K., Pannasch, U., and Kettenmann, H. (2005). Dopamine and noradrenaline control distinct functions in rodent microglial cells. Mol. Cell. Neurosci. 29, 128-138.
50. Fathi, Z., Iben, L. G., and Parker, E. M. (1995). Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype. Neurochem. Res. 20, 107-113.
51. Filippini, G., Brusaferri, F., Sibley, W. A., Citterio, A., Ciucci, G., Midgard, R., et al. (2000). Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst. Rev. 4, CD001331.
52. Fletcher, J. M., Lalor, S. J., Sweeney, C. M., Tubridy, N., and Mills, K. H. (2010). T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin. Exp. Immunol. 162, 1-11.
53. Frischer, J. M., Bramow, S., Dal-Bianco, A., Lucchinetti, C. F., Rauschka, H., Schmidbauer, M., et al. (2009). The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 132, 1175-1189.
54. Frohman, E. M., Eagar, T., Monson, N., Stuve, O., and Karandikar, N. (2008). Immunologic mechanisms of multiple sclerosis. Neuroimaging Clin. N. Am. 18, 577-588.
55. Frohman, E. M., Filippi, M., Stuve, O., Waxman, S. G., Corboy, J., Phillips, J. T., et al. (2005). Characterizing the mechanisms of progression in multiple sclerosis: evidence and new hypotheses for future directions. Arch. Neurol. 62, 1345-1356.
56. Frohman, E. M., Racke, M. K., and Raine, C. S. (2006). Multiple sclerosis - the plaque and its pathogenesis. N. Engl. J. Med. 354, 942-955.
57. Fu, L., Matthews, P. M., De Stefano, N., Worsley, K. J., Narayanan, S., Francis, G. S., et al. (1998). Imaging axonal damage of normal-appearing white matter in multiple sclerosis. Brain 121(Pt 1), 103-113.
58. Gandhi, R., Laroni, A., and Weiner, H. L. (2010). Role of the innate immune system in the pathogenesis of multiple sclerosis. J. Neuroimmunol. 221, 7-14.
59. Gantz, I., Miwa, H., Konda, Y., Shimoto, Y., Tashiro, T., Watson, S. J., et al. (1993). Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J. Biol. Chem. 268, 15174-15179.
60. Gautron, L., Lee, C., Funahashi, H., Friedman, J., Lee, S., and Elmquist, J. (2010). Melanocortin-4 receptor expression in a vago-vagal circuitry involved in postprandial functions. J. Comp. Neurol. 518, 6-24.
61. Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., and Gage, F. H. (2010). Mechanisms underlying inflammation in neurodegeneration. Cell 140, 918-934.
62. Gold, S. M., and Heesen, C. (2006). Stress and disease progression in multiple sclerosis and its animal models. Neuroimmunomodulation 13, 318-326.
63. Gold, S. M., Raji, A., Huitinga, I., Wiedemann, K., Schulz, K. H., and Heesen, C. (2005a). Hypothalamo-pituitary-adrenal axis activity predicts disease progression in multiple sclerosis. J. Neuroimmunol. 165, 186-191.
64. Gold, S. M., Mohr, D. C., Huitinga, I., Flachenecker, P., Sternberg, E. M., and Heesen, C. (2005b). The role of stress-response systems for the pathogenesis and progression of MS. Trends Immunol. 26, 644-652.
65. Gothert, M. (1984). Facilitatory effect of adrenocorticotropic hormone and related peptides on Ca2+-dependent noradrenaline release from sympathetic nerves. Neuroscience 11, 1001-1009.
66. Gottschalk, M., Kümpfel, T., Flachenecker, P., Uhr, M., Trenkwalder, C., Holsboer, F., et al. (2005). Fatigue and regulation of the hypothalamo-pituitary-adrenal axis in multiple sclerosis. Arch. Neurol. 62, 277-280.
67. Guarini, S., Cainazzo, M. M., Giuliani, D., Mioni, C., Altavilla, D., Marini, H., et al. (2004). Adrenocorticotropin reverses hemorrhagic shock in anesthetized rats through the rapid activation of a vagal anti-inflammatory pathway. Cardiovasc. Res. 63, 357-365.
68. Haddad, J. J., Saadé, N. E., and Safieh-Garabedian, B. (2002). Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary-adrenal revolving axis. J. Neuroimmunol. 133, 1-19.
69. Haitina, T., Klovins, J., Takahashi, A., Löwgren, M., Ringholm, A., Enberg, J., et al. (2007). Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes. BMC Evol. Biol. 7:101. doi:10.1186/1471-2148-7-101
70. Harp, C. T., Ireland, S., Davis, L. S., Remington, G., Cassidy, B., Cravens, P. D., et al. (2010). Memory B cells from a subset of treatment-naive relapsing-remitting multiple sclerosis patients elicit CD4(+) T-cell proliferation and IFN-gamma production in response to myelin basic protein and myelin oligodendrocyte glycoprotein. Eur. J. Immunol. 40, 2942-2956.
71. Haskó, G., Szabó, C., Németh, Z. H., and Deitch, E. A. (2002). Dopamine suppresses IL-12 p40 production by lipopolysaccharide-stimulated macrophages via a beta-adrenoceptor-mediated mechanism. J. Neuroimmunol. 122, 34-39.
72. Hauser, S. L., and Oksenberg, J. R. (2006). The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 52, 61-76.
73. Heesen, C., Gold, S. M., Raji, A., Wiedemann, K., and Schulz, K. H. (2002). Cognitive impairment correlates with hypothalamo-pituitary-adrenal axis dysregulation in multiple sclerosis. Opt. Lett. 27, 505-517.
74. Heinig, J. A., Keeley, F. W., Robson, P., Sower, S. A., and Youson, J. H. (1995). The appearance of proopiomelanocortin early in vertebrate evolution: cloning and sequencing of POMC from a Lamprey pituitary cDNA library. Gen. Comp. Endocrinol. 99, 137-144.
75. Hollifield, R. D., Harbige, L. S., Pham-Dinh, D., and Sharief, M. K. (2003). Evidence for cytokine dysregulation in multiple sclerosis: peripheral blood mononuclear cell production of pro-inflammatory and anti-inflammatory cytokines during relapse and remission. Autoimmunity 36, 133-141.
76. H.P. Acthar® Gel (2011). (Repository Corticotropin Injection) [Prescribing Information]. Hayward, CA: Questcor Pharmaceuticals, Inc.
77. Huitinga, I., Erkut, Z. A., van Beurden, D., and Swaab, D. F. (2003). The hypothalamo-pituitary-adrenal axis in multiple sclerosis. Ann. N. Y. Acad. Sci. 992, 118-128.
78. Huitinga, I., Erkut, Z. A., van Beurden, D., and Swaab, D. F. (2004). Impaired hypothalamus-pituitary-adrenal axis activity and more severe multiple sclerosis with hypothalamic lesions. Ann. Neurol. 55, 37-45.
79. Ichiyama, T., Sakai, T., Catania, A., Barsh, G. S., Furukawa, S., and Lipton, J. M. (1999a). Inhibition of peripheral NF-kappaB activation by central action of alpha-melanocyte-stimulating hormone. J. Neuroimmunol. 99, 211-217.
80. Ichiyama, T., Sakai, T., Catania, A., Barsh, G. S., Furukawa, S., and Lipton, J. M. (1999b). Systemically administered alpha-melanocyte-stimulating peptides inhibit NF-kappaB activation in experimental brain inflammation. Brain Res. 836, 31-37.
81. Jacobson, L. (2005). Hypothalamic-pituitary-adrenocortical axis regulation. Endocrinol. Metab. Clin. North Am. 34, 271-292.
82. Johnson, E. W., Hughes, T. K. Jr., and Smith, E. M. (2001). ACTH receptor distribution and modulation among murine mononuclear leukocyte populations. J. Biol. Regul. Homeost. Agents 15, 156-162.
83. Kermode, A. G., Thompson, A. J., Tofts, P., MacManus, D. G., Kendall, B. E., Kingsley, D. P., et al. (1990). Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain 113(Pt 5), 1477-1489.
84. Khoury, S. J., Healy, B. C., Kivisäkk, P., Viglietta, V., Egorova, S., Guttmann, C. R., et al. (2010). A randomized controlled double-masked trial of albuterol add-on therapy in patients with multiple sclerosis. Arch. Neurol. 67, 1055-1061.
85. Kishi, T., Aschkenasi, C. J., Lee, C. E., Mountjoy, K. G., Saper, C. B., and Elmquist, J. K. (2003). Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J. Comp. Neurol. 457, 213-235.
86. Klovins, J., Haitina, T., Fridmanis, D., Kilianova, Z., Kapa, I., Fredriksson, R., et al. (2004). The melanocortin system in Fugu: determination of POMC/AGRP/MCR gene repertoire and synteny, as well as pharmacology and anatomical distribution of the MCRs. Mol. Biol. Evol. 21, 563-579.
87. Kuenz, B., Lutterotti, A., Ehling, R., Gneiss, C., Haemmerle, M., Rainer, C., et al. (2008). Cerebrospinal fluid B cells correlate with early brain inflammation in multiple sclerosis. PLoS ONE 3:e2559. doi:10.1371/journal.pone.0002559
88. Kutzelnigg, A., Lucchinetti, C. F., Stadelmann, C., Brück, W., Rauschka, H., Bergmann, M., et al. (2005). Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128, 2705-2712.
89. Lassmann, H. (2007). Multiple sclerosis: is there neurodegeneration independent from inflammation? J. Neurol. Sci. 259, 3-6.
90. Lassmann, H., Brück, W., and Lucchinetti, C. F. (2007). The immunopathology of multiple sclerosis: an overview. Brain Pathol. 17, 210-218.
91. Limone, P., Ferrero, B., Calvelli, P., Del Rizzo, P., Rota, E., Berardi, C., et al. (2002). Hypothalamic-pituitary-adrenal axis function and cytokine production in multiple sclerosis with or without interferon-beta treatment. Acta Neurol. Scand. 105, 372-377.
92. Lindskog, A., Ebefors, K., Johansson, M. E., Stefánsson, B., Granqvist, A., Arnadottir, M., et al. (2010). Melanocortin 1 receptor agonists reduce proteinuria. J. Am. Soc. Nephrol. 21, 1290-1298.
93. Lublin, F. D., Baier, M., and Cutter, G. (2003). Effect of relapses on development of residual deficit in multiple sclerosis. Neurology 61, 1528-1532.
94. Lublin, F. D., and Reingold, S. C. (1996). Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46, 907-911.
95. Luger, T. A., and Brzoska, T. (2007). Alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. Ann. Rheum. Dis. 66(Suppl. 3), iii52-iii55.
96. Lyons, P. R., Newman, P. K., and Saunders, M. (1988). Methylprednisolone therapy in multiple sclerosis: a profile of adverse effects. J. Neurol. Neurosurg. Psychiatr. 51, 285-287.
97. Macaluso, A., McCoy, D., Ceriani, G., Watanabe, T., Biltz, J., Catania, A., et al. (1994). Antiinflammatory influences of alpha-MSH molecules: central neurogenic and peripheral actions. J. Neurosci. 14, 2377-2382.
98. Mackay, M. T., Weiss, S. K., Adams-Webber, T., Ashwal, S., Stephens, D., Ballaban-Gill, K., et al. (2004). Practice parameter: medical treatment of infantile spasms. Report of the American Academy of Neurology and the Child Neurology Society. Neurology 62, 1668-1681.
99. Manna, S. K., and Aggarwal, B. B. (1998). Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. J. Immunol. 161, 2873-2880.
100. Manna, S. K., Sarkar, A., and Sreenivasan, Y. (2006). Alpha-melanocyte-stimulating hormone down-regulates CXC receptors through activation of neutrophil elastase. Eur. J. Immunol. 36, 754-769.
101. Mars, L. T., Saikali, P., Liblau, R. S., and Arbour, N. (2011). Contribution of CD8 T lymphocytes to the immuno-pathogenesis of multiple sclerosis and its animal models. Biochim. Biophys. Acta 1812, 151-161.
102. Mason, M. J., and Van, E. D. (1989). Modulation of IL-1, tumor necrosis factor, and C5a-mediated murine neutrophil migration by alpha-melanocyte-stimulating hormone. J. Immunol. 142, 1646-1651.
103. Mikulkova, Z., Praksova, P., Stourac, P., Bednarik, J., and Michalek, J. (2011). Imbalance in T-cell and cytokine profiles in patients with relapsing-remitting multiple sclerosis. J. Neurol. Sci. 300, 135-141.
104. Morrow, S. A., Metz, L. M., and Kremenchutzky, M. (2009). High dose oral steroids commonly used to treat relapses in Canadian MS clinics. Can. J. Neurol. Sci. 36, 213-215.
105. Nair, A., Frederick, T. J., and Miller, S. D. (2008). Astrocytes in multiple sclerosis: a product of their environment. Cell. Mol. Life Sci. 65, 2702-2720.
106. Namba, K., Kitaichi, N., Nishida, T., and Taylor, A. W. (2002). Induction of regulatory T cells by the immunomodulating cytokines a-melanocyte-stimulating hormone and transforming growth factor-β2. J. Leukoc. Biol. 72, 946-952.
107. Nankova, B., Kvetnansky, R., Hiremagalur, B., Sabban, B., Rusnak, M., and Sabban, E. L. (1996). Immobilization stress elevates gene expression for catecholamine biosynthetic enzymes and some neuropeptides in rat sympathetic ganglia: effects of adrenocorticotropin and glucocorticoids. Endocrinology 137, 5597-5604.
108. National Clinical Advisory Board of the National Multiple Sclerosis Society. (2008). Recommendations Regarding Corticosteroids in the Management of Multiple Sclerosis. New York, NY: National Multiple Sclerosis Society.
109. Nickerson, M., and Marrie, R. M. (2011). Intravenous and oral steroids may be insufficient for treating relapses in a significant proportion of patients with multiple sclerosis: patient experiences collected by NARCOMS [abstract]. Mult. Scler. 17(Suppl. 10), S446.
110. Noseworthy, J. H., Lucchinetti, C., Rodriguez, M., and Weinshenker, B. G. (2000). Multiple sclerosis. N. Engl. J. Med. 343, 938-952.
111. Papadimitriou, A., and Priftis, K. N. (2009). Regulation of the hypothalamic-pituitary-adrenal axis. Neuroimmunomodulation 16, 265-271.
112. Pavlov, V. A., Ochani, M., Gallowitsch-Puerta, M., Ochani, K., Huston, J. M., Czura, C. J., et al. (2006). Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc. Natl. Acad. Sci. U.S.A. 103, 5219-5223.
113. Petzold, A., Eikelenboom, M. J., Keir, G., Grant, D., Lazeron, R. H., Polman, C. H., et al. (2005). Axonal damage accumulates in the progressive phase of multiple sclerosis: three year follow up study. J. Neurol. Neurosurg. Psychiatr. 76, 206-211.
114. Polman, C. H., Reingold, S. C., Banwell, B., Clanet, M., Cohen, J. A., Filippi, M., et al. (2011). Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol. 69, 292-302.
115. Pranzatelli, M. R. (1994). On the molecular mechanism of adrenocorticotrophic hormone in the CNS: neurotransmitters and receptors. Exp. Neurol. 125, 142-161.
116. Prat, A., Biernacki, K., Lavoie, J. F., Poirier, J., Duquette, P., and Antel, J. P. (2002). Migration of multiple sclerosis lymphocytes through brain endothelium. Arch. Neurol. 59, 391-397.
117. Racke, M. K. (2008). The role of B cells in multiple sclerosis: rationale for B-cell-targeted therapies. Curr. Opin. Neurol. 21(Suppl. 1), S9-S18.
118. Redondo, P., García-Foncillas, J., Okroujnov, I., and Bandrés, E. (1998). Alpha-MSH regulates interleukin-10 expression by human keratinocytes. Arch. Dermatol. Res. 290, 425-428.
119. Richman, D. P., and Arnason, B. G. (1979). Nicotinic acetylcholine receptor: evidence for a functionally distinct receptor on human lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 76, 4632-4635.
120. Sandman, C. A., and Kastin, A. J. (1981). The influence of fragments of the LPH chains on learning, memory and attention in animals and man. Pharmacol. Ther. 13, 39-60.
121. Scholzen, T. E., Sunderkötter, C., Kalden, D. H., Brzoska, T., Fastrich, M., Fisbeck, T., et al. (2003). Alpha-melanocyte stimulating hormone prevents lipopolysaccharide-induced vasculitis by down-regulating endothelial cell adhesion molecule expression. Endocrinology 144, 360-370.
122. Schorr, E. C., and Arnason, B. G. (1999). Interactions between the sympathetic nervous system and the immune system. Brain Behav. Immun. 13, 271-278.
123. Serova, L. I., Gueorguiev, V., Cheng, S. Y., and Sabban, E. L. (2008). Adrenocorticotropic hormone elevates gene expression for catecholamine biosynthesis in rat superior cervical ganglia and locus coeruleus by an adrenal independent mechanism. Neuroscience 153, 1380-1389.
124. Shytle, R. D., Mori, T., Townsend, K., Vendrame, M., Sun, N., Zeng, J., et al. (2004). Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors. J. Neurochem. 89, 337-343.
125. Sibley, W. A. (2009). Spotlight series: pivotal trials through today's knowledge - adrenocorticotropic hormone. Int. MS J. 16, 42-46.
126. Sloka, J. S., and Stefanelli, M. (2005). The mechanism of action of methylprednisolone in the treatment of multiple sclerosis. Mult. Scler. 11, 425-432.
127. Sorensen, T. L., Tani, M., Jensen, J., Pierce, V., Lucchinetti, C., Folcik, V. A., et al. (1999). Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J. Clin. Invest. 103, 807-815.
128. Stafstrom, C. E., Arnason, B. G., Baram, T. Z., Catania, A., Cortez, M. A., Glauser, T. A., et al. (2011). Treatment of infantile spasms: emerging insights from clinical and basic science perspectives. J. Child Neurol. 26, 1411-1421.
129. Strand, F. L., and Kung, T. T. (1980). ACTH accelerates recovery of neuromuscular function following crushing of peripheral nerve. Peptides 1, 135-138.
130. Suzuki, I., Cone, R. D., Im, S., Nordlund, J., and Abdel-Malek, Z. A. (1996). Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis. Endocrinology 137, 1627-1633.
131. Szabo, B., Hedler, L., and Starke, K. (1989). Facilitation of the release of noradrenaline: an extra-adrenal effect of adrenocorticotropic hormone. Resuscitation 18, 229-242.
132. Taherzadeh, S., Sharma, S., Chhajlani, V., Gantz, I., Rajora, N., Demitri, M. T., et al. (1999). Alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages. Am. J. Physiol. 276, R1289-R1294.
133. Takahashi, A., and Kawauchi, H. (2006). Evolution of melanocortin systems in fish. Gen. Comp. Endocrinol. 148, 85-94.
134. Taylor, A., and Namba, K. (2001). In vitro induction of CD25+CD4+regulatory T cells by the neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH). Immunol. Cell Biol. 79, 358-367.
135. Taylor, A. W., and Kitaichi, N. (2008). The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) therapy. Brain Behav. Immun. 22, 639-646.
136. Then Bergh, F., Grasser, A., Trenkwalder, C., Backmund, H., Holsboer, F., and Rupprecht, R. (1999a). Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis. J. Neurol. 246, 292-298.
137. Then Bergh, F., Kümpfel, T., Trenkwalder, C., Rupprecht, R., and Holsboer, F. (1999b). Dysregulation of the hypothalamo-pituitary-adrenal axis is related to the clinical course of MS. Neurology 53, 772-777.
138. Then Bergh, F., Kümpfel, T., Schumann, E., Held, U., Schwan, M., Blazevic, M., et al. (2006). Monthly intravenous methylprednisolone in relapsing-remitting multiple sclerosis - reduction of enhancing lesions, T2 lesion volume and plasma prolactin concentrations. BMC Neurol. 6:19. doi:10.1186/1471-2377-6-19
139. Thrower, B. W. (2009). Relapse management in multiple sclerosis. Neurologist 15, 1-5.
140. Trapp, B. D., Peterson, J., Ransohoff, R. M., Rudick, R., Mörk, S., and Bö, L. (1998). Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med. 338, 278-285.
141. Turnbull, A. V., and Rivier, C. L. (1999). Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol. Rev. 79, 1-71.
142. van der Neut, R., Hol, E. M., Gispen, W. H., and Bär, P. R. (1992). Stimulation by melanocortins of neurite outgrowth from spinal and sensory neurons in vitro. Peptides 13, 1109-1115.
143. Venken, K., Hellings, N., Hensen, K., Rummens, J. L., Medaer, R., D'hooghe, M. B., et al. (2006). Secondary progressive in contrast to relapsing-remitting multiple sclerosis patients show a normal CD4+CD25+ regulatory T-cell function and FOXP3 expression. J. Neurosci. Res. 83, 1432-1446.
144. Vollmer, T. (2007). The natural history of relapses in multiple sclerosis. J. Neurol. Sci. 256(Suppl. 1), S5-S13.
145. Wan, S., Browning, K. N., Coleman, F. H., Sutton, G., Zheng, H., Butler, A., et al. (2008). Presynaptic melanocortin-4 receptors on vagal afferent fibers modulate the excitability of rat nucleus tractus solitarius neurons. J. Neurosci. 28, 4957-4966.
146. Wandinger, K. P., Wessel, K., Trillenberg, P., Heindl, N., and Kirchner, H. (1998). Effect of high-dose methylprednisolone administration on immune functions in multiple sclerosis patients. Acta Neurol. Scand. 97, 359-365.
147. Waugh, D. J., and Wilson, C. (2008). The interleukin-8 pathway in cancer. Clin. Cancer Res. 14, 6735-6741.
148. Weber, M. S., and Hemmer, B. (2010). Cooperation of B cells and T cells in the pathogenesis of multiple sclerosis. Results Probl. Cell Differ. 51, 115-126.
149. Weber, M. S., Prod'homme, T., Patarroyo, J. C., Molnarfi, N., Karnezis, T., Lehmann-Horn, K., et al. (2010). B-cell activation influences T-cell polarization and outcome of anti-CD20 B-cell depletion in central nervous system autoimmunity. Ann. Neurol. 68, 369-383.
150. Wiegmann, K., Muthyala, S., Kim, D. H., Arnason, B. G., and Chelmicka-Schorr, E. (1995). Beta-adrenergic agonists suppress chronic/relapsing experimental allergic encephalomyelitis (CREAE) in Lewis rats. J. Neuroimmunol. 56, 201-206.
151. Wilson, E. H., Weninger, W., and Hunter, C. A. (2010). Trafficking of immune cells in the central nervous system. J. Clin. Invest. 120, 1368-1379.
152. Wootla, B., Denic, A., Keegan, B. M., Winters, J. L., Astapenko, D., Warrington, A. E., et al. (2011). Evidence for the role of B cells and immunoglobulins in the pathogenesis of multiple sclerosis. Neurol. Res. Int. 2011, 780712.
153. Xia, Y., Wikberg, J. E., and Chhajlani, V. (1995). Expression of melanocortin 1 receptor in periaqueductal gray matter. Neuroreport 6, 2193-2196.
154. Yan, J., and Greer, J. M. (2008). NF-kappa B, a potential therapeutic target for the treatment of multiple sclerosis. CNS Neurol. Disord. Drug Targets 7, 536-557.
155. Yoon, S. W., Goh, S. H., Chun, J. S., Cho, E. W., Lee, M. K., Kim, K. L., et al. (2003). alpha-Melanocyte-stimulating hormone inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production in leukocytes by modulating protein kinase A, p38 kinase, and nuclear factor kappa B signaling pathways. J. Biol. Chem. 278, 32914-32920.
156. Ysrraelit, M. C., Gaitán, M. I., Lopez, A. S., and Correale, J. (2008). Impaired hypothalamic-pituitary-adrenal axis activity in patients with multiple sclerosis. Neurology 71, 1948-1954.
157. Zaidi, M., Sun, L., Robinson, L. J., Tourkova, I. L., Liu, L., Wang, Y., et al. (2010). ACTH protects against glucocorticoid-induced osteonecrosis of bone. Proc. Natl. Acad. Sci. U.S.A. 107, 8782-8787.
158. Zivadinov, R., Rudick, R. A., De Masi, R., Nasuelli, D., Ukmar, M., Pozzi-Mucelli, R. S., et al. (2001). Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS. Neurology 57, 1239-1247.
159. Zivadinov, R., Zorzon, M., De Masi, R., Nasuelli, D., and Cazzato, G. (2008). Effect of intravenous methylprednisolone on the number, size and confluence of plaques in relapsing-remitting multiple sclerosis. J. Neurol. Sci. 267, 28-35.