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Glucocorticoid effects on the immune system

W Winn Chatham, MD
Section Editors
Jordan S Orange, MD, PhD
Kieren A Marr, MD
Deputy Editors
Anna M Feldweg, MD
Sheila Bond, MD


Glucocorticoids (corticosteroids) have inhibitory effects on a broad range of immune responses. Because of their inhibitory effects on multiple types of immune cells, glucocorticoids are remarkably efficacious in managing many of the acute disease manifestations of inflammatory and autoimmune disorders [1].

The mechanisms of action of glucocorticoids upon the various effector cells of the immune system, as well as the effect of glucocorticoids on infection risk and vaccination, will be reviewed here. The effects of glucocorticoids on other specific physiologic systems are presented separately:

(See "Major side effects of systemic glucocorticoids".)

(See "Prevention and treatment of glucocorticoid-induced osteoporosis".)

(See "Glucocorticoid-induced myopathy".)

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Literature review current through: Nov 2017. | This topic last updated: Apr 19, 2017.
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  1. Chatham WW, Kimberly RP. Treatment of lupus with corticosteroids. Lupus 2001; 10:140.
  2. Zhang G, Zhang L, Duff GW. A negative regulatory region containing a glucocorticosteroid response element (nGRE) in the human interleukin-1beta gene. DNA Cell Biol 1997; 16:145.
  3. Scheinman RI, Cogswell PC, Lofquist AK, Baldwin AS Jr. Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science 1995; 270:283.
  4. Almawi WY, Beyhum HN, Rahme AA, Rieder MJ. Regulation of cytokine and cytokine receptor expression by glucocorticoids. J Leukoc Biol 1996; 60:563.
  5. Auphan N, DiDonato JA, Rosette C, et al. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 1995; 270:286.
  6. Göttlicher M, Heck S, Herrlich P. Transcriptional cross-talk, the second mode of steroid hormone receptor action. J Mol Med (Berl) 1998; 76:480.
  7. Karin M, Liu Zg, Zandi E. AP-1 function and regulation. Curr Opin Cell Biol 1997; 9:240.
  8. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med 2005; 353:1711.
  9. Tobler A, Meier R, Seitz M, et al. Glucocorticoids downregulate gene expression of GM-CSF, NAP-1/IL-8, and IL-6, but not of M-CSF in human fibroblasts. Blood 1992; 79:45.
  10. Borson DB, Gruenert DC. Glucocorticoids induce neutral endopeptidase in transformed human tracheal epithelial cells. Am J Physiol 1991; 260:L83.
  11. Flower RJ, Blackwell GJ. Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature 1979; 278:456.
  12. Blackwell GJ, Carnuccio R, Di Rosa M, et al. Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids. Nature 1980; 287:147.
  13. Hirata F, Schiffmann E, Venkatasubramanian K, et al. A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci U S A 1980; 77:2533.
  14. Kim SW, Rhee HJ, Ko J, et al. Inhibition of cytosolic phospholipase A2 by annexin I. Specific interaction model and mapping of the interaction site. J Biol Chem 2001; 276:15712.
  15. Lew W, Oppenheim JJ, Matsushima K. Analysis of the suppression of IL-1 alpha and IL-1 beta production in human peripheral blood mononuclear adherent cells by a glucocorticoid hormone. J Immunol 1988; 140:1895.
  16. Chen CC, Sun YT, Chen JJ, Chiu KT. TNF-alpha-induced cyclooxygenase-2 expression in human lung epithelial cells: involvement of the phospholipase C-gamma 2, protein kinase C-alpha, tyrosine kinase, NF-kappa B-inducing kinase, and I-kappa B kinase 1/2 pathway. J Immunol 2000; 165:2719.
  17. Hammerschmidt DE, White JG, Craddock PR, Jacob HS. Corticosteroids inhibit complement-induced granulocyte aggregation. A possible mechanism for their efficacy in shock states. J Clin Invest 1979; 63:798.
  18. Youssef P, Roberts-Thomson P, Ahern M, Smith M. Pulse methylprednisolone in rheumatoid arthritis: effects on peripheral blood and synovial fluid neutrophil surface phenotype. J Rheumatol 1995; 22:2065.
  19. Fan PT, Yu DT, Targoff C, Bluestone R. Effect of corticosteroids on the human immune response. Suppression of mitogen-induced lymphocyte proliferation by "pulse" methylprednisolone. Transplantation 1978; 26:266.
  20. Fan PT, Yu DT, Clements PJ, et al. Effect of corticosteroids on the human immune response: comparison of one and three daily 1 gm intravenous pulses of methylprednisolone. J Lab Clin Med 1978; 91:625.
  21. Barak M, Cohen A, Herschkowitz S. Total leukocyte and neutrophil count changes associated with antenatal betamethasone administration in premature infants. Acta Paediatr 1992; 81:760.
  22. Shoenfeld Y, Gurewich Y, Gallant LA, Pinkhas J. Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis. Am J Med 1981; 71:773.
  23. Olnes MJ, Kotliarov Y, Biancotto A, et al. Effects of Systemically Administered Hydrocortisone on the Human Immunome. Sci Rep 2016; 6:23002.
  24. Fauci AS, Dale DC, Balow JE. Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med 1976; 84:304.
  25. Boumpas DT, Chrousos GP, Wilder RL, et al. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 1993; 119:1198.
  26. Fauci AS, Murakami T, Brandon DD, et al. Mechanisms of corticosteroid action on lymphocyte subpopulations. VI. Lack of correlation between glucocorticosteroid receptors and the differential effects of glucocorticosteroids on T-cell subpopulations. Cell Immunol 1980; 49:43.
  27. Cox G. Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J Immunol 1995; 154:4719.
  28. Meagher LC, Cousin JM, Seckl JR, Haslett C. Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. J Immunol 1996; 156:4422.
  29. Schleimer RP, Freeland HS, Peters SP, et al. An assessment of the effects of glucocorticoids on degranulation, chemotaxis, binding to vascular endothelium and formation of leukotriene B4 by purified human neutrophils. J Pharmacol Exp Ther 1989; 250:598.
  30. Jones CJ, Morris KJ, Jayson MI. Prednisolone inhibits phagocytosis by polymorphonuclear leucocytes via steroid receptor mediated events. Ann Rheum Dis 1983; 42:56.
  31. Herzer P, Lemmel EM. Inhibition of granulocyte function by prednisolone and non-steroid anti-inflammatory drugs. Quantitative evaluation with NBT test and its correlation with phagocytosis. Immunobiology 1980; 157:78.
  32. Rinehart JJ, Sagone AL, Balcerzak SP, et al. Effects of corticosteroid therapy on human monocyte function. N Engl J Med 1975; 292:236.
  33. Rinehart JJ, Balcerzak SP, Sagone AL, LoBuglio AF. Effects of corticosteroids on human monocyte function. J Clin Invest 1974; 54:1337.
  34. Atkinson JP, Frank MM. Complement-independent clearance of IgG-sensitized erythrocytes: inhibition by cortisone. Blood 1974; 44:629.
  35. Gerlag DM, Haringman JJ, Smeets TJ, et al. Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in rheumatoid arthritis. Arthritis Rheum 2004; 50:3783.
  36. Balow JE, Rosenthal AS. Glucocorticoid suppression of macrophage migration inhibitory factor. J Exp Med 1973; 137:1031.
  37. Gerrard TL, Cupps TR, Jurgensen CH, Fauci AS. Hydrocortisone-mediated inhibition of monocyte antigen presentation: dissociation of inhibitory effect and expression of DR antigens. Cell Immunol 1984; 85:330.
  38. van de Garde MD, Martinez FO, Melgert BN, et al. Chronic exposure to glucocorticoids shapes gene expression and modulates innate and adaptive activation pathways in macrophages with distinct changes in leukocyte attraction. J Immunol 2014; 192:1196.
  39. Eddy JL, Krukowski K, Janusek L, Mathews HL. Glucocorticoids regulate natural killer cell function epigenetically. Cell Immunol 2014; 290:120.
  40. Slade JD, Hepburn B. Prednisone-induced alterations of circulating human lymphocyte subsets. J Lab Clin Med 1983; 101:479.
  41. Settipane GA, Pudupakkam RK, McGowan JH. Corticosteroid effect on immunoglobulins. J Allergy Clin Immunol 1978; 62:162.
  42. Lack G, Ochs HD, Gelfand EW. Humoral immunity in steroid-dependent children with asthma and hypogammaglobulinemia. J Pediatr 1996; 129:898.
  43. Posey WC, Nelson HS, Branch B, Pearlman DS. The effects of acute corticosteroid therapy for asthma on serum immunoglobulin levels. J Allergy Clin Immunol 1978; 62:340.
  44. Fedor ME, Rubinstein A. Effects of long-term low-dose corticosteroid therapy on humoral immunity. Ann Allergy Asthma Immunol 2006; 97:113.
  45. Levy AL, Waldmann TA. The effect of hydrocortisone on immunoglobulin metabolism. J Clin Invest 1970; 49:1679.
  46. Jabara HH, Ahern DJ, Vercelli D, Geha RS. Hydrocortisone and IL-4 induce IgE isotype switching in human B cells. J Immunol 1991; 147:1557.
  47. Butler WT, Rossen RD. Effects of corticosteroids on immunity in man. I. Decreased serum IgG concentration caused by 3 or 5 days of high doses of methylprednisolone. J Clin Invest 1973; 52:2629.
  48. Hamilos DL, Young RM, Peter JB, et al. Hypogammaglobulinemia in asthmatic patients. Ann Allergy 1992; 68:472.
  49. Berger W, Pollock J, Kiechel F, et al. Immunoglobulin levels in children with chronic severe asthma. Ann Allergy 1978; 41:67.
  50. Haynes BF, Fauci AS. The differential effect of in vivo hydrocortisone on the kinetics of subpopulations of human peripheral blood thymus-derived lymphocytes. J Clin Invest 1978; 61:703.
  51. Horst HJ, Flad HD. Corticosteroid-interleukin 2 interactions: inhibition of binding of interleukin 2 to interleukin 2 receptors. Clin Exp Immunol 1987; 68:156.
  52. Paliogianni F, Ahuja SS, Balow JP, et al. Novel mechanism for inhibition of human T cells by glucocorticoids. Glucocorticoids inhibit signal transduction through IL-2 receptor. J Immunol 1993; 151:4081.
  53. Hanson JA, Sohaib SA, Newell-Price J, et al. Computed tomography appearance of the thymus and anterior mediastinum in active Cushing's syndrome. J Clin Endocrinol Metab 1999; 84:602.
  54. Cohen JJ, Duke RC. Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J Immunol 1984; 132:38.
  55. Lanza L, Scudeletti M, Puppo F, et al. Prednisone increases apoptosis in in vitro activated human peripheral blood T lymphocytes. Clin Exp Immunol 1996; 103:482.
  56. Webster JC, Huber RM, Hanson RL, et al. Dexamethasone and tumor necrosis factor-alpha act together to induce the cellular inhibitor of apoptosis-2 gene and prevent apoptosis in a variety of cell types. Endocrinology 2002; 143:3866.
  57. McKinley L, Alcorn JF, Peterson A, et al. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J Immunol 2008; 181:4089.
  58. Ramesh R, Kozhaya L, McKevitt K, et al. Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids. J Exp Med 2014; 211:89.
  59. Franchimont D, Louis E, Dewe W, et al. Effects of dexamethasone on the profile of cytokine secretion in human whole blood cell cultures. Regul Pept 1998; 73:59.
  60. Ashwell JD, Lu FW, Vacchio MS. Glucocorticoids in T cell development and function*. Annu Rev Immunol 2000; 18:309.
  61. Visser J, van Boxel-Dezaire A, Methorst D, et al. Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro. Blood 1998; 91:4255.
  62. BOVORNKITTI S, KANGSADAL P, SATHIRAPAT P, OONSOMBATTI P. Reversion and reconversion rate of tuberculin skin reactions in correction with the use of prednisone. Dis Chest 1960; 38:51.
  63. Wallen N, Kita H, Weiler D, Gleich GJ. Glucocorticoids inhibit cytokine-mediated eosinophil survival. J Immunol 1991; 147:3490.
  64. Andersen V, bro-Rasmussen F, Hougaard K. Autoradiographic studies of eosinophil kinetics: Effects of cortisol. Cell Tissue Kinet 1969; 2:139.
  65. Nagase H, Miyamasu M, Yamaguchi M, et al. Glucocorticoids preferentially upregulate functional CXCR4 expression in eosinophils. J Allergy Clin Immunol 2000; 106:1132.
  66. Kita H, Abu-Ghazaleh R, Sanderson CJ, Gleich GJ. Effect of steroids on immunoglobulin-induced eosinophil degranulation. J Allergy Clin Immunol 1991; 87:70.
  67. Andrade MV, Hiragun T, Beaven MA. Dexamethasone suppresses antigen-induced activation of phosphatidylinositol 3-kinase and downstream responses in mast cells. J Immunol 2004; 172:7254.
  68. Nakamura R, Okunuki H, Ishida S, et al. Gene expression profiling of dexamethasone-treated RBL-2H3 cells: induction of anti-inflammatory molecules. Immunol Lett 2005; 98:272.
  69. Park SK, Beaven MA. Mechanism of upregulation of the inhibitory regulator, src-like adaptor protein (SLAP), by glucocorticoids in mast cells. Mol Immunol 2009; 46:492.
  70. Shodell M, Shah K, Siegal FP. Circulating human plasmacytoid dendritic cells are highly sensitive to corticosteroid administration. Lupus 2003; 12:222.
  71. Woltman AM, Massacrier C, de Fijter JW, et al. Corticosteroids prevent generation of CD34+-derived dermal dendritic cells but do not inhibit Langerhans cell development. J Immunol 2002; 168:6181.
  72. Strangfeld A, Eveslage M, Schneider M, et al. Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient? Ann Rheum Dis 2011; 70:1914.
  73. Chen JY, Wang LK, Feng PH, et al. Risk of Shingles in Adults with Primary Sjogren's Syndrome and Treatments: A Nationwide Population-Based Cohort Study. PLoS One 2015; 10:e0134930.
  74. Sakuma Y, Katoh T, Owada K, et al. Initial functional status predicts infections during steroid therapy for renal diseases. Clin Nephrol 2005; 63:68.
  75. Pappas DA, Hooper MM, Kremer JM, et al. Herpes Zoster Reactivation in Patients With Rheumatoid Arthritis: Analysis of Disease Characteristics and Disease-Modifying Antirheumatic Drugs. Arthritis Care Res (Hoboken) 2015; 67:1671.
  76. Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis 1989; 11:954.
  77. Ginzler E, Diamond H, Kaplan D, et al. Computer analysis of factors influencing frequency of infection in systemic lupus erythematosus. Arthritis Rheum 1978; 21:37.
  78. Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum 2006; 54:628.
  79. Waljee AK, Rogers MA, Lin P, et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ 2017; 357:j1415.
  80. Spika JS, Halsey NA, Fish AJ, et al. Serum antibody response to pneumococcal vaccine in children with nephrotic syndrome. Pediatrics 1982; 69:219.
  81. Lahood N, Emerson SS, Kumar P, Sorensen RU. Antibody levels and response to pneumococcal vaccine in steroid-dependent asthma. Ann Allergy 1993; 70:289.
  82. Herron A, Dettleff G, Hixon B, et al. Influenza vaccination in patients with rheumatic diseases. Safety and efficacy. JAMA 1979; 242:53.
  83. Kubiet MA, Gonzalez-Rothi RJ, Cottey R, Bender BS. Serum antibody response to influenza vaccine in pulmonary patients receiving corticosteroids. Chest 1996; 110:367.
  84. Winston DJ, Ho WG, Schiffman G, et al. Pneumococcal vaccination of recipients of bone marrow transplants. Arch Intern Med 1983; 143:1735.