Glucocorticoids—All-Rounders Tackling the Versatile Players of the Immune System
Open accessAbstract
Glucocorticoids regulate fundamental processes of the human body and control cellular functions such as cell metabolism, growth, differentiation, and apoptosis. Moreover, endogenous glucocorticoids link the endocrine and immune system and ensure the correct function of inflammatory events during tissue repair, regeneration, and pathogen elimination via genomic and rapid non-genomic pathways. Due to their strong immunosuppressive, anti-inflammatory and anti-allergic effects on immune cells, tissues and organs, glucocorticoids significantly improve the quality of life of many patients suffering from diseases caused by a dysregulated immune system. Despite the multitude and seriousness of glucocorticoid-related adverse events including diabetes mellitus, osteoporosis and infections, these agents remain indispensable, representing the most powerful, and cost-effective drugs in the treatment of a wide range of rheumatic diseases. These include rheumatoid arthritis, vasculitis, and connective tissue diseases, as well as many other pathological conditions of the immune system. Depending on the therapeutically affected cell type, glucocorticoid actions strongly vary among different diseases. While immune responses always represent complex reactions involving different cells and cellular processes, specific immune cell populations with key responsibilities driving the pathological mechanisms can be identified for certain autoimmune diseases. In this review, we will focus on the mechanisms of action of glucocorticoids on various leukocyte populations, exemplarily portraying different autoimmune diseases as heterogeneous targets of glucocorticoid actions: (i) Abnormalities in the innate immune response play a crucial role in the initiation and perpetuation of giant cell arteritis (GCA). (ii) Specific types of CD4+ T helper (Th) lymphocytes, namely Th1 and Th17 cells, represent important players in the establishment and course of rheumatoid arthritis (RA), whereas (iii) B cells have emerged as central players in systemic lupus erythematosus (SLE). (iv) Allergic reactions are mainly triggered by several different cytokines released by activated Th2 lymphocytes. Using these examples, we aim to illustrate the versatile modulating effects of glucocorticoids on the immune system. In contrast, in the treatment of lymphoproliferative disorders the pro-apoptotic action of glucocorticoids prevails, but their mechanisms differ depending on the type of cancer. Therefore, we will also give a brief insight into the current knowledge of the mode of glucocorticoid action in oncological treatment focusing on leukemia.
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Glucocorticoids often precipitate significant hyperglycaemia.
“Despite their therapeutic value, they carry significant metabolic risks, including osteoporosis, hypertension, dyslipidaemia and hyperglycaemia. 3 , 4 , 5 , 6 , 7”
From A systematic review of glucocorticoid use in type 1 diabetes: Glycaemic effects and clinical management strategies (2026) · cites this paper as [4]
The SLE section reports diabetes mellitus among adverse effects attributed to glucocorticoid treatment, and the Introduction says adverse events become more frequent with higher doses and longer use. These passages support a risk of glucose-related harm, but do not establish that glucocorticoids often precipitate significant hyperglycaemia. Page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredGlucocorticoids remain indispensable for the management of many autoimmune and inflammatory conditions, but their use is often complicated by metabolic side effects.
“GCs remain indispensable for the management of many autoimmune and inflammatory conditions; however, their use is often complicated by metabolic side effects.”
From A systematic review of glucocorticoid use in type 1 diabetes: Glycaemic effects and clinical management strategies (2026) · cites this paper as [4]
Appropriate concentrations of cortisol are essential for normal neurodevelopment and function, as well as cognitive processes such as learning and memory.
“Appropriate concentrations of cortisol are essential for normal neurodevelopment and function, as well as cognitive processes such as learning and memory, and studies have shown that microbes modulate the HPA axis throughout life.”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [139]
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COVID-19 infection and rheumatoid arthritis: Faraway, so close
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Central regulation of stress-evoked peripheral immune responses
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- Authors
- Strehl, C., Ehlers, L., Gaber, T., & Buttgereit, F.
- Affiliations
- German Rheumatism Research Centre (DE)
- Corresponding author
- Strehl, Cindy
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2019-07-24
- Volume
- 10
- Pages
- 1744-1744
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC6667663
- OpenAlex
- W2957947066
- Cited by
- 308
- References
- 281
- Citations by year
- 2026: 38 · 2025: 39 · 2024: 53 · 2023: 58 · 2022: 46 · 2021: 45 · 2020: 27 · 2019: 2
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Refubium (Universitätsbibliothek der Freien Universität Berlin) (submittedVersion, cc-by)
- Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver (cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (353142848)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- glucocorticoids, immunosuppression, anti-inflammatory activity, autoimmune disease, rheumatoid arthritis, giant cell arteritis, Th17 cells, Th1 cells, systemic lupus erythematosus, B cells, allergic reactions, Th2 cells, lymphoproliferative disorders, leukemia, glucocorticoid adverse effects, glucocorticoid receptor
- MeSH terms
- Arthritis, Rheumatoid, Glucocorticoids, Humans, Lupus Erythematosus, Systemic, Giant Cell Arteritis, Th1 Cells, Th17 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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