Glucocorticoid effects on the immune system
- W Winn Chatham, MD
W Winn Chatham, MD
- Professor of Medicine
- University of Alabama at Birmingham
- Section Editors
- E Richard Stiehm, MD
E Richard Stiehm, MD
- Editor-in-Chief — Allergy and Immunology
- Section Editor — Immunology and Immunodeficiency
- Distinguished Research Professor of Pediatrics
- David Geffen School of Medicine at UCLA
- Kieren A Marr, MD
Kieren A Marr, MD
- Section Editor — Compromised Host Infections; Fungal Infections
- Professor of Medicine and Oncology
- Johns Hopkins University School of Medicine
Glucocorticoids (corticosteroids) have inhibitory effects on a broad range of specific immune responses mediated by T cells and B cells, as well as potent suppressive effects on the effector functions of phagocytes. Because of their inhibitory effects on both acquired and innate immunologic function, glucocorticoids are remarkably efficacious in managing many of the acute disease manifestations of inflammatory and autoimmune disorders .
The mechanisms of action of glucocorticoids upon the various effector cells of the adaptive and innate immune system will be reviewed here. The effects of glucocorticoids on other specific physiologic systems are presented separately. (See "Major side effects of systemic glucocorticoids" and "Pathogenesis, clinical features, and evaluation of glucocorticoid-induced osteoporosis" and "Glucocorticoid effects on the nervous system and behavior" and "Glucocorticoid therapy in septic shock".)
OVERVIEW OF INTRACELLULAR EFFECTS
Glucocorticoids diffuse passively across the cellular membrane and bind to the intracellular glucocorticoid receptor. Binding of the drug to this receptor results in translocation of the complex into the nucleus, where it can interact directly with specific DNA sequences (glucocorticoid-responsive elements [GREs]), and other transcription factors.
Effects on gene transcription — Binding of the receptor to GREs may result in either enhancement or suppression of transcription of susceptible downstream genes. The antiinflammatory effects of glucocorticoids result from the following:
●Binding to and blocking promoter sites of pro-inflammatory genes, such as interleukin-1alpha (IL-1alpha) and interleukin-1beta (IL-1beta) .
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- OVERVIEW OF INTRACELLULAR EFFECTS
- Effects on gene transcription
- Effects on post-translational events
- EFFECTS ON LEUKOCYTE TRAFFICKING
- EFFECTS ON INNATE IMMUNITY
- - Neutrophils
- - Eosinophils
- - Monocytes and macrophages
- Mast cells and basophils
- Effects on pro-inflammatory mediators
- EFFECTS ON ACQUIRED IMMUNITY
- Dendritic cells and macrophages
- T cells
- - Effects on T cell selection
- - T cell lineage commitment
- B cells and antibody production
- Impact on vaccination
- IMPACT OF DOSE
- Low-to-moderate doses
- Higher doses
- INFECTION RISK
- Types of infections
- Measures to reduce risk
- HETEROGENEITY IN GLUCOCORTICOID SENSITIVITY
- SUMMARY AND RECOMMENDATIONS