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Critical Reviews™ in Immunology

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Traditional Concepts and Future Avenues of Glucocorticoid Action in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis Therapy

Volume 29, Issue 3, 2009, pp. 255-273
DOI: 10.1615/CritRevImmunol.v29.i3.50
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Fred Luhder
Institute for Multiple Sclerosis Research, University of Göttingen and Gemeinnützige Hertie-Stiftung, Waldweg 33, 37073 Göttingen, Germany
Holger Reichardt
Institute of Cellular and Molecular Immunology, University of Goettingen Medical School

ABSTRACT

Glucocorticoids (GCs) constitute one of the oldest families of anti-inflammatory and immunosuppressive drugs. Since their first clinical use more than half a century ago, they have been employed for therapeutic invention in a variety of conditions, including atopic disorders, autoimmune diseases, and cancer. Nevertheless, their exact mechanism of action is still incompletely understood. In this review, we elaborate especially on the mechanism of GCs in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), and summarize our current knowledge on how therapeutic and endogenous GCs impact the pathogenesis of EAE and MS. This includes findings obtained from genetically modified mice and rats lacking or overexpressing the GC receptor (GR) in specific cell types, and the analysis of new pharmaceutical formulations and chemical GC modifications aimed at improving treatment efficacy and specificity. Stimulated by these recent developments, it can be anticipated that novel therapeutic regimens will find their way into clinical practice for the benefit of affected patients.

KEY WORDS: glucocorticoids, glucocorticoid receptor, EAE, multiple sclerosis, liposomes
CITED BY

  1. Kimbrough Dorlan J., Fujihara Kazuo, Jacob Anu, Lana-Peixoto Marco A., Isabel Leite Maria, Levy Michael, Marignier Romain, Nakashima Ichiro, Palace Jacqueline, de Seze Jérôme, Stuve Olaf, Tenembaum Silvia N., Traboulsee Anthony, Waubant Emmanuelle, Weinshenker Brian G., Wingerchuk Dean M., Treatment of neuromyelitis optica: Review and recommendations, Multiple Sclerosis and Related Disorders, 1, 4, 2012. Crossref

  2. Klotz L., Knolle P., Nuclear receptors: TH 17 cell control from within, FEBS Letters, 585, 23, 2011. Crossref

  3. Glass Christopher K., Saijo Kaoru, Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells, Nature Reviews Immunology, 10, 5, 2010. Crossref

  4. Hermann-Kleiter Natascha, Baier Gottfried, Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4+ T cell effector functions, Cell Communication and Signaling, 12, 1, 2014. Crossref

  5. Guo Jintao, Waknine-Grinberg Judith H., Mitchell Andrew J., Barenholz Yechezkel, Golenser Jacob, Reduction of Experimental Cerebral Malaria and Its Related Proinflammatory Responses by the Novel Liposome-Basedβ-Methasone Nanodrug, BioMed Research International, 2014, 2014. Crossref

  6. Lühder F., Lee D.H., Gold R., Stegbauer J., Linker R.A., Small but powerful: Short peptide hormones and their role in autoimmune inflammation, Journal of Neuroimmunology, 217, 1-2, 2009. Crossref

  7. Schweingruber N., Reichardt S. D., Lühder F., Reichardt H. M., Mechanisms of Glucocorticoids in the Control of Neuroinflammation, Journal of Neuroendocrinology, 24, 1, 2012. Crossref

  8. Mix Eilhard, Meyer-Rienecker Hans, Hartung Hans-Peter, Zettl Uwe K., Animal models of multiple sclerosis—Potentials and limitations, Progress in Neurobiology, 92, 3, 2010. Crossref

  9. Liu Yu-mei, Liu Xi-jun, Bai Sha-Sha, Mu Li-li, Kong Qing-fei, Sun Bo, Wang Dan-dan, Wang Jing-hua, Shu Shi, Wang Guang-you, Li Hu-lun, The effect of electroacupuncture on T cell responses in rats with experimental autoimmune encephalitis, Journal of Neuroimmunology, 220, 1-2, 2010. Crossref

  10. Kleiter Ingo, Gold Ralf, Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders, Neurotherapeutics, 13, 1, 2016. Crossref

  11. Waknine-Grinberg Judith H., Even-Chen Simcha, Avichzer Jasmine, Turjeman Keren, Bentura-Marciano Annael, Haynes Richard K., Weiss Lola, Allon Nahum, Ovadia Haim, Golenser Jacob, Barenholz Yechezkel, Coban Cevayir, Glucocorticosteroids in Nano-Sterically Stabilized Liposomes Are Efficacious for Elimination of the Acute Symptoms of Experimental Cerebral Malaria, PLoS ONE, 8, 8, 2013. Crossref

  12. Jongen Peter Joseph, Stavrakaki Ioanna, Voet Bernard, Hoogervorst Erwin, van Munster Erik, Linssen Wim H., Sinnige Ludovicus G., Verhagen Wim I., Visser Leo H., van der Kruijk Ruud, Verheul Freek, Boringa Jan, Heerings Marco, Gladdines Werner, Lönnqvist Fredrik, Gaillard Pieter, Patient-reported adverse effects of high-dose intravenous methylprednisolone treatment: a prospective web-based multi-center study in multiple sclerosis patients with a relapse, Journal of Neurology, 263, 8, 2016. Crossref

  13. Montes-Cobos Elena, Ring Sarah, Fischer Henrike J., Heck Joachim, Strauß Judith, Schwaninger Markus, Reichardt Sybille D., Feldmann Claus, Lühder Fred, Reichardt Holger M., Targeted delivery of glucocorticoids to macrophages in a mouse model of multiple sclerosis using inorganic-organic hybrid nanoparticles, Journal of Controlled Release, 245, 2017. Crossref

  14. Montes-Cobos Elena, Schweingruber Nils, Li Xiao, Fischer Henrike J., Reichardt Holger M., Lühder Fred, Deletion of the Mineralocorticoid Receptor in Myeloid Cells Attenuates Central Nervous System Autoimmunity, Frontiers in Immunology, 8, 2017. Crossref

  15. Werneck Lineu Cesar, Lorenzoni Paulo José, Radünz Vitor A, Utiumi Marco A.T, Kay Cláudia Suemi Kamoi, Scola Rosana Herminia, Influence of treatment in multiple sclerosis dysability: an open, retrospective, non-randomized long-term analysis, Arquivos de Neuro-Psiquiatria, 68, 4, 2010. Crossref

  16. Zhang Qian, Xu Chuncao, Lin Shiqi, Zhou Huanbin, Yao Gangtao, Liu Hu, Wang Lili, Pan Xin, Quan Guilan, Wu Chuanbin, Synergistic immunoreaction of acupuncture-like dissolving microneedles containing thymopentin at acupoints in immune-suppressed rats, Acta Pharmaceutica Sinica B, 8, 3, 2018. Crossref

  17. Tischner Denise, Theiss Jennifer, Karabinskaya Anna, van den Brandt Jens, Reichardt Sybille D., Karow Ulrike, Herold Marco J., Lühder Fred, Utermöhlen Olaf, Reichardt Holger M., Acid Sphingomyelinase Is Required for Protection of Effector Memory T Cells against Glucocorticoid-Induced Cell Death, The Journal of Immunology, 187, 9, 2011. Crossref

  18. Schweingruber Nils, Haine Axel, Tiede Karsten, Karabinskaya Anna, van den Brandt Jens, Wüst Simone, Metselaar Josbert M., Gold Ralf, Tuckermann Jan P., Reichardt Holger M., Lühder Fred, Liposomal Encapsulation of Glucocorticoids Alters Their Mode of Action in the Treatment of Experimental Autoimmune Encephalomyelitis, The Journal of Immunology, 187, 8, 2011. Crossref

  19. Hoepner Robert, Bagnoud Maud, Pistor Maximilian, Salmen Anke, Briner Myriam, Synn Helen, Schrewe Lisa, Guse Kirsten, Ahmadi Farhad, Demir Seray, Laverick Louis, Gresle Melissa, Worley Paul, Reichardt Holger Michael, Butzkueven Helmut, Gold Ralf, Metz Imke, Lühder Fred, Chan Andrew, Vitamin D increases glucocorticoid efficacy via inhibition of mTORC1 in experimental models of multiple sclerosis, Acta Neuropathologica, 138, 3, 2019. Crossref

  20. Fischer Henrike J., Finck Tobias L. K., Pellkofer Hannah L., Reichardt Holger M., Lühder Fred, Glucocorticoid Therapy of Multiple Sclerosis Patients Induces Anti-inflammatory Polarization and Increased Chemotaxis of Monocytes, Frontiers in Immunology, 10, 2019. Crossref

  21. Gili-Kovács Judit, Hoepner Robert, Salmen Anke, Bagnoud Maud, Gold Ralf, Chan Andrew, Briner Myriam, An algorithm using clinical data to predict the optimal individual glucocorticoid dosage to treat multiple sclerosis relapses, Therapeutic Advances in Neurological Disorders, 14, 2021. Crossref

  22. Miljković Željka, Momčilović Miljana, Miljković Djordje, Mostarica-Stojković Marija, Methylprednisolone inhibits IFN-γ and IL-17 expression and production by cells infiltrating central nervous system in experimental autoimmune encephalomyelitis, Journal of Neuroinflammation, 6, 1, 2009. Crossref

  23. Radandish Maedeh, Khalilian Parvin, Esmaeil Nafiseh, The Role of Distinct Subsets of Macrophages in the Pathogenesis of MS and the Impact of Different Therapeutic Agents on These Populations, Frontiers in Immunology, 12, 2021. Crossref

  24. König Lisa, Szczesny Sabine, Brixius-Anderko Simone, Bernhardt Rita, Hannemann Frank, Mixed-culture fermentation for enhanced C21-hydroxylation of glucocorticoids, Journal of Biotechnology, 314-315, 2020. Crossref

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