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Glucocorticoids: Immunity and Inflammation

  • Simona Ronchetti
  • Carlo Riccardi
Chapter

Abstract

As very powerful anti-inflammatory and immunosuppressive drugs, glucocorticoids have gained attention over the past decades as a first line treatment for chronic inflammatory and autoimmune diseases, in addition to its wide use in the field of oncology. An extensive body of research has accumulated with regards to the molecular anti-inflammatory mechanisms by which glucocorticoids exert their effects on the cells of the immune system. Moreover, some pro-inflammatory properties have recently emerged, based on the analysis of glucocorticoid-regulated genes. Understanding the physiology and the pharmacology of these hormones and drugs in the context of inflammation and the immune system will allow for the comprehension of their still incomplete function in homeostasis and of their practical clinical applications.

Keywords

Glucocorticoid Inflammation Immunosuppression Stress HPA axis Lymphocytes 

References

  1. 1.
    Nicolaides NC, Kyratzi E, Lamprokostopoulou A, Chrousos GP, Charmandari E (2015) Stress, the stress system and the role of glucocorticoids. Neuroimmunomodulation 22(1–2):6–19CrossRefPubMedGoogle Scholar
  2. 2.
    Nguyen ET, Streicher J, Berman S, Caldwell JL, Ghisays V, Estrada CM, Wulsin AC, Solomon MB (2017) A mixed glucocorticoid/mineralocorticoid receptor modulator dampens endocrine and hippocampal stress responsivity in male rats. Physiol Behav 178:82–92CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Charmandari E, Tsigos C, Chrousos G (2005) Endocrinology of the stress response. Annu Rev Physiol 67:259–284CrossRefPubMedGoogle Scholar
  4. 4.
    Vyas S, Rodrigues AJ, Silva JM, Tronche F, Almeida OF, Sousa N, Sotiropoulos I (2016) Chronic stress and glucocorticoids: from neuronal plasticity to neurodegeneration. Neural Plast 2016:6391686CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Sousa N, Almeida OF (2012) Disconnection and reconnection: the morphological basis of (mal)adaptation to stress. Trends Neurosci 35(12):742–751CrossRefPubMedGoogle Scholar
  6. 6.
    Mak JC, Nishikawa M, Shirasaki H, Miyayasu K, Barnes PJ (1995) Protective effects of a glucocorticoid on downregulation of pulmonary beta 2-adrenergic receptors in vivo. J Clin Invest 96(1):99–106CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Sakaue M, Hoffman BB (1991) Glucocorticoids induce transcription and expression of the alpha 1B adrenergic receptor gene in DTT1 MF-2 smooth muscle cells. J Clin Invest 88(2):385–389CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ogawa K, Hirai M, Katsube T, Murayama M, Hamaguchi K, Shimakawa T, Naritake Y, Hosokawa T, Kajiwara T (2000) Suppression of cellular immunity by surgical stress. Surgery 127(3):329–336CrossRefPubMedGoogle Scholar
  9. 9.
    Salicru AN, Sams CF, Marshall GD (2007) Cooperative effects of corticosteroids and catecholamines upon immune deviation of the type-1/type-2 cytokine balance in favor of type-2 expression in human peripheral blood mononuclear cells. Brain Behav Immun 21(7):913–920CrossRefPubMedGoogle Scholar
  10. 10.
    Xiang L, Marshall GD Jr (2013) Immunomodulatory effects of dexamethasone on gene expression of cytokine and stress hormone receptors in peripheral blood mononuclear cells. Int Immunopharmacol 17(3):556–560CrossRefPubMedGoogle Scholar
  11. 11.
    Chida Y, Sudo N, Sonoda J, Hiramoto T, Kubo C (2007) Early-life psychological stress exacerbates adult mouse asthma via the hypothalamus-pituitary-adrenal axis. Am J Respir Crit Care Med 175(4):316–322CrossRefPubMedGoogle Scholar
  12. 12.
    Miyasaka T, Dobashi-Okuyama K, Takahashi T, Takayanagi M, Ohno I (2017) The interplay between neuroendocrine activity and psychological stress-induced exacerbation of allergic asthma. Allergol Int 67:32–42CrossRefPubMedGoogle Scholar
  13. 13.
    DeKruyff RH, Fang Y, Umetsu DT (1998) Corticosteroids enhance the capacity of macrophages to induce Th2 cytokine synthesis in CD4+ lymphocytes by inhibiting IL-12 production. J Immunol 160(5):2231–2237PubMedGoogle Scholar
  14. 14.
    Olsen PC, Kitoko JZ, Ferreira TP, de- Azevedo CT, Arantes AC, Martins MA (2015) Glucocorticoids decrease Treg cell numbers in lungs of allergic mice. Eur J Pharmacol 747:52–58CrossRefPubMedGoogle Scholar
  15. 15.
    Freier E, Weber CS, Nowottne U, Horn C, Bartels K, Meyer S, Hildebrandt Y, Luetkens T, Cao Y, Pabst C, Muzzulini J, Schnee B, Brunner-Weinzierl MC, Marangolo M, Bokemeyer C, Deter HC, Atanackovic D (2010) Decrease of CD4(+)FOXP3(+) T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor. Psychoneuroendocrinology 35(5):663–673CrossRefPubMedGoogle Scholar
  16. 16.
    Sierra A, Gottfried-Blackmore A, Milner TA, McEwen BS, Bulloch K (2008) Steroid hormone receptor expression and function in microglia. Glia 56(6):659–674CrossRefPubMedGoogle Scholar
  17. 17.
    Nair A, Bonneau RH (2006) Stress-induced elevation of glucocorticoids increases microglia proliferation through NMDA receptor activation. J Neuroimmunol 171(1–2):72–85CrossRefPubMedGoogle Scholar
  18. 18.
    Frank MG, Miguel ZD, Watkins LR, Maier SF (2010) Prior exposure to glucocorticoids sensitizes the neuroinflammatory and peripheral inflammatory responses to E. coli lipopolysaccharide. Brain Behav Immun 24(1):19–30CrossRefPubMedGoogle Scholar
  19. 19.
    Goujon E, Parnet P, Laye S, Combe C, Kelley KW, Dantzer R (1995) Stress downregulates lipopolysaccharide-induced expression of proinflammatory cytokines in the spleen, pituitary, and brain of mice. Brain Behav Immun 9(4):292–303CrossRefPubMedGoogle Scholar
  20. 20.
    Frank MG, Weber MD, Watkins LR, Maier SF (2016) Stress-induced neuroinflammatory priming: a liability factor in the etiology of psychiatric disorders. Neurobiol Stress 4:62–70CrossRefPubMedGoogle Scholar
  21. 21.
    Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wohleb ES, McKim DB, Sheridan JF, Godbout JP (2014) Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior. Front Neurosci 8:447PubMedGoogle Scholar
  23. 23.
    Cohen S, Janicki-Deverts D, Doyle WJ, Miller GE, Frank E, Rabin BS, Turner RB (2012) Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci U S A 109(16):5995–5999CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Dhabhar FS (2009) Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation 16(5):300–317CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ronaldson A, Gazali AM, Zalli A, Kaiser F, Thompson SJ, Henderson B, Steptoe A, Carvalho L (2016) Increased percentages of regulatory T cells are associated with inflammatory and neuroendocrine responses to acute psychological stress and poorer health status in older men and women. Psychopharmacology (Berl) 233(9):1661–1668CrossRefGoogle Scholar
  26. 26.
    Mundy-Bosse BL, Thornton LM, Yang HC, Andersen BL, Carson WE (2011) Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients. Cell Immunol 270(1):80–87CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Stark JL, Avitsur R, Hunzeker J, Padgett DA, Sheridan JF (2002) Interleukin-6 and the development of social disruption-induced glucocorticoid resistance. J Neuroimmunol 124(1–2):9–15CrossRefPubMedGoogle Scholar
  28. 28.
    Eiro N, Vizoso FJ (2012) Inflammation and cancer. World J Gastrointest Surg 4(3):62–72CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    De Rosa V, Di Rella F, Di Giacomo A, Matarese G (2017) Regulatory T cells as suppressors of anti-tumor immunity: role of metabolism. Cytokine Growth Factor Rev 35:15–25CrossRefPubMedGoogle Scholar
  30. 30.
    Chaudhary B, Elkord E (2016) Regulatory T cells in the tumor microenvironment and cancer progression: role and therapeutic targeting. Vaccines (Basel). 2016 Aug 6;4(3). pii: E28. https://doi.org/10.3390/vaccines4030028 CrossRefPubMedCentralGoogle Scholar
  31. 31.
    Darrasse-Jeze G, Podsypanina K (2013) How numbers, nature, and immune status of foxp3(+) regulatory T-cells shape the early immunological events in tumor development. Front Immunol 4:292CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Powell ND, Tarr AJ, Sheridan JF (2013) Psychosocial stress and inflammation in cancer. Brain Behav Immun 30(Suppl):S41–S47CrossRefPubMedGoogle Scholar
  33. 33.
    Ayroldi E, Zollo O, Bastianelli A, Marchetti C, Agostini M, Di Virgilio R, Riccardi C (2007) GILZ mediates the antiproliferative activity of glucocorticoids by negative regulation of Ras signaling. J Clin Invest 117(6):1605–1615CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ayroldi E, Petrillo MG, Bastianelli A, Marchetti MC, Ronchetti S, Nocentini G, Ricciotti L, Cannarile L, Riccardi C (2015) L-GILZ binds p53 and MDM2 and suppresses tumor growth through p53 activation in human cancer cells. Cell Death Differ 22(1):118–130CrossRefPubMedGoogle Scholar
  35. 35.
    Dumbell R, Matveeva O, Oster H (2016) Circadian clocks, stress, and immunity. Front Endocrinol 7:37CrossRefGoogle Scholar
  36. 36.
    Cima I, Corazza N, Dick B, Fuhrer A, Herren S, Jakob S, Ayuni E, Mueller C, Brunner T (2004) Intestinal epithelial cells synthesize glucocorticoids and regulate T cell activation. J Exp Med 200(12):1635–1646CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Vacchio MS, Papadopoulos V, Ashwell JD (1994) Steroid production in the thymus: implications for thymocyte selection. J Exp Med 179(6):1835–1846CrossRefPubMedGoogle Scholar
  38. 38.
    Pazirandeh A, Jondal M, Okret S (2005) Conditional expression of a glucocorticoid receptor transgene in thymocytes reveals a role for thymic-derived glucocorticoids in thymopoiesis in vivo. Endocrinology 146(6):2501–2507CrossRefPubMedGoogle Scholar
  39. 39.
    Taves MD, Gomez-Sanchez CE, Soma KK (2011) Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function. Am J Physiol Endocrinol Metab 301(1):E11–E24CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Talaber G, Jondal M, Okret S (2015) Local glucocorticoid production in the thymus. Steroids 103:58–63CrossRefPubMedGoogle Scholar
  41. 41.
    Vacchio MS, Ashwell JD (1997) Thymus-derived glucocorticoids regulate antigen-specific positive selection. J Exp Med 185(11):2033–2038CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Nuotio-Antar AM, Hasty AH, Kovacs WJ (2006) Quantitation and cellular localization of 11beta-HSD1 expression in murine thymus. J Steroid Biochem Mol Biol 99(2–3):93–99CrossRefPubMedGoogle Scholar
  43. 43.
    Taves MD, Plumb AW, Korol AM, Van Der Gugten JG, Holmes DT, Abraham N, Soma KK (2016) Lymphoid organs of neonatal and adult mice preferentially produce active glucocorticoids from metabolites, not precursors. Brain Behav Immun 57:271–281CrossRefPubMedGoogle Scholar
  44. 44.
    Boivin MA, Ye D, Kennedy JC, Al-Sadi R, Shepela C, Ma TY (2007) Mechanism of glucocorticoid regulation of the intestinal tight junction barrier. Am J Physiol Gastrointest Liver Physiol 292(2):G590–G598CrossRefPubMedGoogle Scholar
  45. 45.
    Noti M, Corazza N, Mueller C, Berger B, Brunner T (2010) TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis. J Exp Med 207(5):1057–1066CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Coste A, Dubuquoy L, Barnouin R, Annicotte JS, Magnier B, Notti M, Corazza N, Antal MC, Metzger D, Desreumaux P, Brunner T, Auwerx J, Schoonjans K (2007) LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease. Proc Natl Acad Sci U S A 104(32):13098–13103CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Sidler D, Renzulli P, Schnoz C, Berger B, Schneider-Jakob S, Fluck C, Inderbitzin D, Corazza N, Candinas D, Brunner T (2012) Colon cancer cells produce immunoregulatory glucocorticoids. Oncoimmunology 1(4):529–530CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Kostadinova F, Schwaderer J, Sebeo V, Brunner T (2014) Why does the gut synthesize glucocorticoids? Ann Med 46(7):490–497CrossRefPubMedGoogle Scholar
  49. 49.
    Hostettler N, Bianchi P, Gennari-Moser C, Kassahn D, Schoonjans K, Corazza N, Brunner T (2012) Local glucocorticoid production in the mouse lung is induced by immune cell stimulation. Allergy 67(2):227–234CrossRefPubMedGoogle Scholar
  50. 50.
    Herold MJ, McPherson KG, Reichardt HM (2006) Glucocorticoids in T cell apoptosis and function. Cell Mol Life Sci 63(1):60–72CrossRefPubMedGoogle Scholar
  51. 51.
    Stephens GL, Ashwell JD, Ignatowicz L (2003) Mutually antagonistic signals regulate selection of the T cell repertoire. Int Immunol 15(5):623–632CrossRefPubMedGoogle Scholar
  52. 52.
    Mittelstadt PR, Monteiro JP, Ashwell JD (2012) Thymocyte responsiveness to endogenous glucocorticoids is required for immunological fitness. J Clin Invest 122(7):2384–2394CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Purton JF, Boyd RL, Cole TJ, Godfrey DI (2000) Intrathymic T cell development and selection proceeds normally in the absence of glucocorticoid receptor signaling. Immunity 13(2):179–186CrossRefPubMedGoogle Scholar
  54. 54.
    Liddicoat DR, Purton JF, Cole TJ, Godfrey DI (2014) Glucocorticoid-mediated repression of T-cell receptor signalling is impaired in glucocorticoid receptor exon 2-disrupted mice. Immunol Cell Biol 92(2):148–155CrossRefPubMedGoogle Scholar
  55. 55.
    Baumann S, Dostert A, Novac N, Bauer A, Schmid W, Fas SC, Krueger A, Heinzel T, Kirchhoff S, Schutz G, Krammer PH (2005) Glucocorticoids inhibit activation-induced cell death (AICD) via direct DNA-dependent repression of the CD95 ligand gene by a glucocorticoid receptor dimer. Blood 106(2):617–625CrossRefPubMedGoogle Scholar
  56. 56.
    Lowenberg M, Tuynman J, Bilderbeek J, Gaber T, Buttgereit F, van Deventer S, Peppelenbosch M, Hommes D (2005) Rapid immunosuppressive effects of glucocorticoids mediated through Lck and Fyn. Blood 106(5):1703–1710CrossRefPubMedGoogle Scholar
  57. 57.
    Banuelos J, Lu NZ (2016) A gradient of glucocorticoid sensitivity among helper T cell cytokines. Cytokine Growth Factor Rev 31:27–35CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Schewitz-Bowers LP, Lait PJ, Copland DA, Chen P, Wu W, Dhanda AD, Vistica BP, Williams EL, Liu B, Jawad S, Li Z, Tucker W, Hirani S, Wakabayashi Y, Zhu J, Sen N, Conway-Campbell BL, Gery I, Dick AD, Wei L, Nussenblatt RB, Lee RW (2015) Glucocorticoid-resistant Th17 cells are selectively attenuated by cyclosporine A. Proc Natl Acad Sci U S A 112(13):4080–4085CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Elenkov IJ (2004) Glucocorticoids and the Th1/Th2 balance. Ann N Y Acad Sci 1024:138–146CrossRefPubMedGoogle Scholar
  60. 60.
    Chen X, Oppenheim JJ, Winkler-Pickett RT, Ortaldo JR, Howard OM (2006) Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+)CD4(+)CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur J Immunol 36(8):2139–2149CrossRefPubMedGoogle Scholar
  61. 61.
    Xiang L, Marshall GD Jr (2011) Immunomodulatory effects of in vitro stress hormones on FoxP3, Th1/Th2 cytokine and costimulatory molecule mRNA expression in human peripheral blood mononuclear cells. Neuroimmunomodulation 18(1):1–10CrossRefPubMedGoogle Scholar
  62. 62.
    Bereshchenko O, Coppo M, Bruscoli S, Biagioli M, Cimino M, Frammartino T, Sorcini D, Venanzi A, Di Sante M, Riccardi C (2014) GILZ promotes production of peripherally induced Treg cells and mediates the crosstalk between glucocorticoids and TGF-beta signaling. Cell Rep 7(2):464–475CrossRefPubMedGoogle Scholar
  63. 63.
    Kruth KA, Fang MM, Shelton DN, Abu-Halawa O, Mahling R, Yang HX, Weissman JS, Loh ML, Muschen M, Tasian SK, Bassik MC, Kampmann M, Pufall MA (2017) Suppression of B-cell development genes is key to glucocorticoid efficacy in treatment of acute lymphoblastic leukemia. Blood 129(22):3000–3008CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Gruver-Yates AL, Quinn MA, Cidlowski JA (2014) Analysis of glucocorticoid receptors and their apoptotic response to dexamethasone in male murine B cells during development. Endocrinology 155(2):463–474CrossRefPubMedGoogle Scholar
  65. 65.
    Bruscoli S, Biagioli M, Sorcini D, Frammartino T, Cimino M, Sportoletti P, Mazzon E, Bereshchenko O, Riccardi C (2015) Lack of glucocorticoid-induced leucine zipper (GILZ) deregulates B-cell survival and results in B-cell lymphocytosis in mice. Blood 126(15):1790–1801CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Alnemri ES, Fernandes TF, Haldar S, Croce CM, Litwack G (1992) Involvement of BCL-2 in glucocorticoid-induced apoptosis of human pre-B-leukemias. Cancer Res 52(2):491–495PubMedGoogle Scholar
  67. 67.
    Chalubinski M, Grzegorczyk J, Kowalski ML (2011) Glucocorticoid-induced immunoglobulin E synthesis by peripheral blood mononuclear cells from allergic and nonallergic subjects. Ann Allergy Asthma Immunol 107(3):251–257CrossRefPubMedGoogle Scholar
  68. 68.
    Baschant U, Tuckermann J (2010) The role of the glucocorticoid receptor in inflammation and immunity. J Steroid Biochem Mol Biol 120(2–3):69–75CrossRefPubMedGoogle Scholar
  69. 69.
    Barczyk K, Ehrchen J, Tenbrock K, Ahlmann M, Kneidl J, Viemann D, Roth J (2010) Glucocorticoids promote survival of anti-inflammatory macrophages via stimulation of adenosine receptor A3. Blood 116(3):446–455CrossRefPubMedGoogle Scholar
  70. 70.
    Zhong HJ, Wang HY, Yang C, Zhou JY, Jiang JX (2013) Low concentrations of corticosterone exert stimulatory effects on macrophage function in a manner dependent on glucocorticoid receptors. Int J Endocrinol 2013:405127CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Wang J, Arase H (2014) Regulation of immune responses by neutrophils. Ann N Y Acad Sci 1319:66–81CrossRefPubMedGoogle Scholar
  72. 72.
    Ricci E, Ronchetti S, Pericolini E, Gabrielli E, Cari L, Gentili M, Roselletti E, Migliorati G, Vecchiarelli A, Riccardi C (2017) Role of the glucocorticoid-induced leucine zipper gene in dexamethasone-induced inhibition of mouse neutrophil migration via control of annexin A1 expression. FASEB J 31(7):3054–3065CrossRefPubMedGoogle Scholar
  73. 73.
    Stroncek DF, Yau YY, Oblitas J, Leitman SF (2001) Administration of G--CSF plus dexamethasone produces greater granulocyte concentrate yields while causing no more donor toxicity than G--CSF alone. Transfusion 41(8):1037–1044CrossRefPubMedGoogle Scholar
  74. 74.
    Meagher LC, Cousin JM, Seckl JR, Haslett C (1996) Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. J Immunol 156(11):4422–4428PubMedGoogle Scholar
  75. 75.
    Druilhe A, Letuve S, Pretolani M (2003) Glucocorticoid-induced apoptosis in human eosinophils: mechanisms of action. Apoptosis 8(5):481–495CrossRefPubMedGoogle Scholar
  76. 76.
    Fulkerson PC, Rothenberg ME (2013) Targeting eosinophils in allergy, inflammation and beyond. Nat Rev Drug Discov 12(2):117–129CrossRefPubMedGoogle Scholar
  77. 77.
    Yamaguchi M, Hirai K, Nakajima K, Ohtoshi T, Takaishi T, Ohta K, Morita Y, Ito K (1994) Dexamethasone inhibits basophil migration. Allergy 49(5):371–375CrossRefPubMedGoogle Scholar
  78. 78.
    Yamagata S, Tomita K, Sano H, Itoh Y, Fukai Y, Okimoto N, Watatani N, Inbe S, Miyajima H, Tsukamoto K, Santoh H, Ichihashi H, Sano A, Sato R, Tohda Y (2012) Non-genomic inhibitory effect of glucocorticoids on activated peripheral blood basophils through suppression of lipid raft formation. Clin Exp Immunol 170(1):86–93CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Oppong E, Flink N, Cato AC (2013) Molecular mechanisms of glucocorticoid action in mast cells. Mol Cell Endocrinol 380(1–2):119–126CrossRefPubMedGoogle Scholar
  80. 80.
    Nilsson G, Butterfield JH, Nilsson K, Siegbahn A (1994) Stem cell factor is a chemotactic factor for human mast cells. J Immunol 153(8):3717–3723PubMedGoogle Scholar
  81. 81.
    Kassel O, Schmidlin F, Duvernelle C, de Blay F, Frossard N (1998) Up- and down-regulation by glucocorticoids of the constitutive expression of the mast cell growth factor stem cell factor by human lung fibroblasts in culture. Mol Pharmacol 54(6):1073–1079CrossRefPubMedGoogle Scholar
  82. 82.
    Bros M, Jahrling F, Renzing A, Wiechmann N, Dang NA, Sutter A, Ross R, Knop J, Sudowe S, Reske-Kunz AB (2007) A newly established murine immature dendritic cell line can be differentiated into a mature state, but exerts tolerogenic function upon maturation in the presence of glucocorticoid. Blood 109(9):3820–3829CrossRefPubMedGoogle Scholar
  83. 83.
    Li CC, Munitic I, Mittelstadt PR, Castro E, Ashwell JD (2015) Suppression of dendritic cell-derived IL-12 by endogenous glucocorticoids is protective in LPS-induced sepsis. PLoS Biol 13(10):e1002269CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Duque Ede A, Munhoz CD (2016) The pro-inflammatory effects of glucocorticoids in the brain. Front Endocrinol 7:78Google Scholar
  85. 85.
    Cruz-Topete D, Cidlowski JA (2015) One hormone, two actions: anti- and pro-inflammatory effects of glucocorticoids. Neuroimmunomodulation 22(1–2):20–32CrossRefPubMedGoogle Scholar
  86. 86.
    Cain DW, Cidlowski JA (2017) Immune regulation by glucocorticoids. Nat Rev Immunol 17(4):233–247CrossRefPubMedGoogle Scholar
  87. 87.
    Sorrells SF, Sapolsky RM (2007) An inflammatory review of glucocorticoid actions in the CNS. Brain Behav Immun 21(3):259–272CrossRefPubMedGoogle Scholar
  88. 88.
    Munhoz CD, Sorrells SF, Caso JR, Scavone C, Sapolsky RM (2010) Glucocorticoids exacerbate lipopolysaccharide-induced signaling in the frontal cortex and hippocampus in a dose-dependent manner. J Neurosci 30(41):13690–13698CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Wiegers GJ, Reul JM (1998) Induction of cytokine receptors by glucocorticoids: functional and pathological significance. Trends Pharmacol Sci 19(8):317–321CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medicine, Section of PharmacologyUniversity of PerugiaPerugiaItaly

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