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Der Anaesthesist Oct 2019Dexamethasone is a synthetic steroid that has been used for many years in the clinical routine due to its anti-inflammatory, anti-allergic and immunosuppressive... (Review)
Review
Dexamethasone is a synthetic steroid that has been used for many years in the clinical routine due to its anti-inflammatory, anti-allergic and immunosuppressive properties. Furthermore, dexamethasone has been used for a long time for prophylaxis and treatment of chemotherapy-induced nausea and vomiting. In the meantime dexamethasone has been approved as standard for the prophylaxis and treatment of postoperative nausea and vomiting (PONV). This review article outlines the indications and side effects of the perioperative administration of dexamethasone.
Topics: Antiemetics; Dexamethasone; Humans; Postoperative Nausea and Vomiting
PubMed: 31595319
DOI: 10.1007/s00101-019-00672-x -
Journal For Immunotherapy of Cancer Jun 2018Corticosteroids are routinely utilized to alleviate edema in patients with intracranial lesions and are first-line agents to combat immune-related adverse events (irAEs)...
BACKGROUND
Corticosteroids are routinely utilized to alleviate edema in patients with intracranial lesions and are first-line agents to combat immune-related adverse events (irAEs) that arise with immune checkpoint blockade treatment. However, it is not known if or when corticosteroids can be administered without abrogating the efforts of immunotherapy. The purpose of this study was to evaluate the impact of dexamethasone on lymphocyte activation and proliferation during checkpoint blockade to provide guidance for corticosteroid use while immunotherapy is being implemented as a cancer treatment.
METHODS
Lymphocyte proliferation, differentiation, and cytokine production were evaluated during dexamethasone exposure. Human T cells were stimulated through CD3 ligation and co-stimulated either directly by CD28 ligation or by providing CD80, a shared ligand for CD28 and CTLA-4. CTLA-4 signaling was inhibited by antibody blockade using ipilimumab which has been approved for the treatment of several solid tumors. The in vivo effects of dexamethasone during checkpoint blockade were evaluated using the GL261 syngeneic mouse intracranial model, and immune populations were profiled by flow cytometry.
RESULTS
Dexamethasone upregulated CTLA-4 mRNA and protein in CD4 and CD8 T cells and blocked CD28-mediated cell cycle entry and differentiation. Naïve T cells were most sensitive, leading to a decrease of the development of more differentiated subsets. Resistance to dexamethasone was conferred by blocking CTLA-4 or providing strong CD28 co-stimulation prior to dexamethasone exposure. CTLA-4 blockade increased IFNγ expression, but not IL-2, in stimulated human peripheral blood T cells exposed to dexamethasone. Finally, we found that CTLA-4 blockade partially rescued T cell numbers in mice bearing intracranial gliomas. CTLA-4 blockade was associated with increased IFNγ-producing tumor-infiltrating T cells and extended survival of dexamethasone-treated mice.
CONCLUSIONS
Dexamethasone-mediated T cell suppression diminishes naïve T cell proliferation and differentiation by attenuating the CD28 co-stimulatory pathway. However, CTLA-4, but not PD-1 blockade can partially prevent some of the inhibitory effects of dexamethasone on the immune response.
Topics: Animals; Dexamethasone; Disease Models, Animal; Female; Humans; Immunosuppression Therapy; Immunotherapy; Mice
PubMed: 29891009
DOI: 10.1186/s40425-018-0371-5 -
ACS Biomaterials Science & Engineering May 2022Dexamethasone (DEX) has been widely used to treat a variety of diseases, including autoimmune diseases, allergies, ocular disorders, cancer, and, more recently,... (Review)
Review
Dexamethasone (DEX) has been widely used to treat a variety of diseases, including autoimmune diseases, allergies, ocular disorders, cancer, and, more recently, COVID-19. However, DEX usage is often restricted in the clinic due to its poor water solubility. When administered through a systemic route, it can elicit severe side effects, such as hypertension, peptic ulcers, hyperglycemia, and hydro-electrolytic disorders. There is currently much interest in developing efficient DEX-loaded nanoformulations that ameliorate adverse disease effects inhibiting advancements in scientific research. Various nanoparticles have been developed to selectively deliver drugs without destroying healthy cells or organs in recent years. In the present review, we have summarized some of the most attractive applications of DEX-loaded delivery systems, including liposomes, polymers, hydrogels, nanofibers, silica, calcium phosphate, and hydroxyapatite. This review provides our readers with a broad spectrum of nanomedicine approaches to deliver DEX safely.
Topics: Dexamethasone; Drug Delivery Systems; Humans; Nanoparticles; COVID-19 Drug Treatment
PubMed: 35439408
DOI: 10.1021/acsbiomaterials.2c00026 -
European Cells & Materials Nov 2019While glucocorticoids have been used for over 50 years to treat rheumatoid and osteoarthritis pain, the prescription of glucocorticoids remains controversial because of... (Review)
Review
While glucocorticoids have been used for over 50 years to treat rheumatoid and osteoarthritis pain, the prescription of glucocorticoids remains controversial because of potentially harmful side effects at the molecular, cellular and tissue levels. One member of the glucocorticoid family, dexamethasone (DEX) has recently been demonstrated to rescue cartilage matrix loss and chondrocyte viability in animal studies and cartilage explant models of tissue injury and post-traumatic osteoarthritis, suggesting the possibility of DEX as a disease-modifying drug if used appropriately. However, the literature on the effects of DEX on cartilage reveals conflicting results on the drug's safety, depending on the dose and duration of DEX exposure as well as the model system used. Overall, DEX has been shown to protect against arthritis-related changes in cartilage structure and function, including matrix loss, inflammation and cartilage viability. These beneficial effects are not always observed in model systems using initially healthy cartilage or isolated chondrocytes, where many studies have reported significant increases in chondrocyte apoptosis. It is crucially important to understand under what conditions DEX may be beneficial or harmful to cartilage and other joint tissues and to determine potential for safe use of this glucocorticoid in the clinic as a disease-modifying drug.
Topics: Animals; Apoptosis; Arthritis; Cartilage; Dexamethasone; Glucocorticoids; Humans
PubMed: 31755076
DOI: 10.22203/eCM.v038a17 -
Journal of the Chinese Medical... Mar 2021The rapid spread of coronavirus disease (COVID-19) in many countries has caused inconvenience in conducting daily life activities, and even deaths. Dexamethasone is a... (Review)
Review
The rapid spread of coronavirus disease (COVID-19) in many countries has caused inconvenience in conducting daily life activities, and even deaths. Dexamethasone is a corticosteroid applied in clinical medicine since 1957, especially in immune therapy fields. Herein, we present the characteristics of Dexamethasone, from molecular mechanisms such as genomic and nongenomic pathways by cellular signal regulations, to clinical applications in various phases of the disease. During COVID-19 pandemic, Dexamethasone given to patients who required oxygen or ventilation therapy showed improved life efficacy.
Topics: Dexamethasone; Humans; Receptors, Glucocorticoid; SARS-CoV-2; Signal Transduction; COVID-19 Drug Treatment
PubMed: 33433137
DOI: 10.1097/JCMA.0000000000000485 -
Cancer Investigation Jul 2022Understanding dexamethasone's effect on the immune microenvironment in glioma patients is of key importance. We performed a comprehensive literature review using the... (Review)
Review
Understanding dexamethasone's effect on the immune microenvironment in glioma patients is of key importance. We performed a comprehensive literature review using the NCBI PubMed database for all articles meeting the following search criteria. ((dexamethasone[All Fields]) AND (glioma or glioblastoma)[Title/Abstract]) AND (immune or T cell or B cell or monocyte or neutrophil or macrophage). Forty-three manuscripts were deemed relevant to the topic at hand. Multiple clinical studies have linked dexamethasone use to decreased overall survival while preclinical studies in murine glioma models have demonstrated decreased tumor-infiltrating lymphocytes after dexamethasone administration.
Topics: Animals; Brain Neoplasms; Dexamethasone; Glioblastoma; Glioma; Humans; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Mice; Precision Medicine; Tumor Microenvironment
PubMed: 34151678
DOI: 10.1080/07357907.2021.1944178 -
Acta Anaesthesiologica Taiwanica :... Sep 2011Postoperative nausea and vomiting (PONV) is a common annoying experience after surgery. The overall incidence of PONV in adults is 20-30%; the incidence rate in patients... (Review)
Review
Postoperative nausea and vomiting (PONV) is a common annoying experience after surgery. The overall incidence of PONV in adults is 20-30%; the incidence rate in patients of high-risk groups can be as high as 70-80%. Children are not exempted from attacking either; the incidence rate in children above the age of 3 is more than 40%. The incidence slowly drops after puberty, sharing the same rate with adults. Dexamethasone can be effective in preventing PONV in adults and children. Compared with other preventive medications, dexamethasone has equal or even better efficacy in reducing the incidence of PONV and has the advantages of low cost and longer effectiveness as well. Although the action mechanism of dexamethasone is hitherto not fully understood, animal studies have confirmed that the vomiting center in the brain stem plays a central role. A combination of dexamethasone with other antiemetics is more effective than any single drug alone. Additionally, the use of dexamethasone to prevent nausea and vomiting triggered by intravenous or epidural morphine for pain control can also offer a good therapeutic effect. To date, clinically, dexamethasone as a preventative drug against PONV has not caused fatal outcome; therefore, it is generally considered to be an effective and safe antiemetic. Nevertheless, its use in this regard may lead to adverse effects, principally postoperative hyperglycemia and infection.
Topics: Antiemetics; Dexamethasone; Drug Therapy, Combination; Humans; Postoperative Nausea and Vomiting; Risk Factors
PubMed: 21982171
DOI: 10.1016/j.aat.2011.06.002 -
Personalized Medicine Jul 2021Immunomodulatory and analgesic effects of dexamethasone are clinically well established, and this synthetic corticosteroid acts as an agonist of glucocorticoid... (Review)
Review
Immunomodulatory and analgesic effects of dexamethasone are clinically well established, and this synthetic corticosteroid acts as an agonist of glucocorticoid receptors. Early results of the RECOVERY Trial from the United Kingdom and others suggest certain benefits of dexamethasone against COVID-19 chronic patients. The efforts have been acknowledged by World Health Organization with an interim guideline to use in patients with a severe and critical illness. The inherent genetic variations in genes such as , , , etc., involved in the pharmacokinetic and pharmacodynamic processes may influence dexamethasone's effects as an anti-inflammatory drug. Besides, the drug may influence transcriptome or metabolic changes in the individuals. In the present review, we summarize the reported genetic variations that impact dexamethasone response and discuss dexamethasone-induced changes in transcriptome and metabolome that may influence potential treatment outcome against COVID-19.
Topics: Animals; COVID-19; Dexamethasone; Drug Repositioning; Female; Gene Frequency; Genetic Variation; Glucocorticoids; Humans; Male; Metabolome; Models, Animal; Pharmaceutical Preparations; Pharmacogenetics; Practice Guidelines as Topic; SARS-CoV-2; Transcriptome; COVID-19 Drug Treatment
PubMed: 34086487
DOI: 10.2217/pme-2020-0183 -
Die Ophthalmologie May 2023
Topics: Vitreoretinal Surgery; Vitreous Body; Dexamethasone
PubMed: 36656386
DOI: 10.1007/s00347-022-01790-5 -
Should dexamethasone be part of routine therapy of bacterial meningitis in industrialised countries?Advances in Experimental Medicine and... 2005Two issues are clear from the data available regarding the current place of dexamethasone in routine management of suspected bacterial meningitis in industrialised... (Review)
Review
Two issues are clear from the data available regarding the current place of dexamethasone in routine management of suspected bacterial meningitis in industrialised countries. First, there is now good evidence of benefit from adjunctive dexamethasone therapy which is not confined to Hib meningitis, but in the case of pneumococcal meningitis probably requires that dexamethasone is given with or before, rather than after, parenteral antibiotics. In meningococcal meningitis, statistically significant benefit has not been demonstrated for any outcome, even in meta-analyses, but the point estimate is in the direction of benefit and failure to demonstrate an effect is more likely to be due to limited power from low event rates rather than no benefit; certainly there is no evidence of a detrimental effect. Most culture-negative cases of presumptive bacterial meningitis outside the neonatal period are likely to be due to one of the above 3 organisms. In the neonatal period or in some settings in developing countries, the spectrum of organisms is very different and extrapolation of these findings cannot be assumed. Second, the suggestion that dexamethasone is not applicable to certain subgroups in industrialised countries (such as cases not treated with cefuroxime, or some other sub-optimal therapy, or cases treated with vancomycin) (5) or that benefit only applies to hearing loss or Hib cases, either do not stand up to scrutiny or are not answerable from available data. What does this mean for clinical practice? The results of randomised controlled trials may not readily translate to clinical practice, particularly with respect to early commencement of steroids. The Sydney data show that in a representative developed country population with good access to services, after controlling for other prognostic variables, early corticosteroid therapy is associated with improved outcome. These data also show that deferred lumbar puncture is frequent and so criteria requiring presumptive identification of an organism are not practical to guide dexamethasone use, indeed those patients in whom lumbar puncture is deferred are more likely to have severe disease. This experience is an important addition to the findings from clinical trials of dexamethasone in pneumococcal meningitis in industrialised countries (5,6) as it demonstrates that adjunctive steroid therapy is beneficial in a 'real world' situation. In addition, the prospect of clinical trials in children, already limited by small case numbers, will be further reduced when the use of the conjugate pneumococcal vaccines is widespread. In Canada, a trend to decreasing use of corticosteroids was noted between 1991 and 1999, probably reflecting conflicting evidence. (16). Unless clear protocols are in place, the commencement of steroids before or with antibiotics will be difficult to implement in emergency situations, as illustrated by the data from Sydney.
Topics: Anti-Inflammatory Agents; Developed Countries; Dexamethasone; Humans; Meningitis, Bacterial; Treatment Outcome
PubMed: 16107073
DOI: 10.1007/0-387-25342-4_13