The early in-vivo effects of a single anti-emetic dose of dexamethasone on innate immune cell gene expression and activation in healthy volunteers
| Autor: | Sophie Wallace, Paul S. Myles, O. Gouldthorpe, Rachael L. Taylor, C. R. Bain, Robert L. Medcalf, Dominik F. Draxler, Tomas Corcoran, Kiymet Bozaoglu |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Real-Time Polymerase Chain Reaction Peripheral blood mononuclear cell Dexamethasone Monocytes Flow cytometry Young Adult 03 medical and health sciences 0302 clinical medicine Antigen 030202 anesthesiology Internal medicine Gene expression medicine Humans Regulation of gene expression Immunity Cellular Innate immune system medicine.diagnostic_test business.industry Healthy Volunteers Immunity Innate 030104 developmental biology Anesthesiology and Pain Medicine Real-time polymerase chain reaction Endocrinology Gene Expression Regulation Leukocytes Mononuclear Antiemetics Cytokines business medicine.drug |
| Zdroj: | Anaesthesia. 73:955-966 |
| ISSN: | 0003-2409 |
| DOI: | 10.1111/anae.14306 |
| Popis: | Dexamethasone is often administered to surgical patients for anti-emetic prophylaxis. This study examined the early (up to 24 h) in-vivo effects of dexamethasone (8 mg) to demonstrate the magnitude and temporal nature of changes on circulating peripheral blood mononuclear cell gene expression and activation in 10 healthy male volunteers. Blood samples were drawn at baseline, 2 h, 4 h and 24 h. Gene expression was measured using quantitative real-time polymerase chain reaction. Cytokine expression was measured using multiplex immuno-assays. Innate immune cell phenotypes were examined with flow cytometry. Dexamethasone resulted in rapid transient changes in immunophilin (p = 0.0247), plasminogen activator inhibitor-1 (p = 0.0004), forkhead box P3 (p = 0.0068) and dual specific phosphatase-1 (p = 0.0157) gene expression at 4 h compared with pre-dexamethasone. Plasma interleukin-10 levels increased within 2 h (p = 0.0071) and returned to baseline at 24 h. Reductions in classical (p = 0.0009) and intermediate monocytes (p = 0.0178) and dendritic cells (p = 0.0012) were followed by increases in the level of these populations at 24 h compared with pre-dexamethasone (classical monocytes p = 0.0073, intermediate monocytes p = 0.0271, dendritic cells p = 0.0142). There was a profound reduction in the mean fluorescence intensity of the maturation marker, human histocompatibility leucocyte antigen, at 24 h in all monocyte subsets (p = 0.0002 for classical and non-classical monocytes, p = 0.0001 for intermediate monocytes) and dendritic cells (p = 0.0001). This study confirms rapid transient effects of 8 mg dexamethasone on innate immune cells with the potential to alter the inflammatory response to surgery and provides support for the hypothesis that intra-operative administration may be both immunosuppressive and immune-activating in the immediate peri-operative period. |
| Databáze: | OpenAIRE |
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