title: Effects of Systemically Administered Hydrocortisone on the Human Immunome.
abstract: Corticosteroids have been used for decades to modulate inflammation therapeutically, yet there is a paucity of data on their effects in humans. We examined the changes in cellular and molecular immune system parameters, or "immunome", in healthy humans after systemic corticosteroid administration. We used multiplexed techniques to query the immunome in 20 volunteers at baseline, and after intravenous hydrocortisone (HC) administered at moderate (250 mg) and low (50 mg) doses, to provide insight into how corticosteroids exert their effects. We performed comprehensive phenotyping of 120 lymphocyte subsets by high dimensional flow cytometry, and observed a decline in circulating specific B and T cell subsets, which reached their nadir 4-8 hours after administration of HC. However, B and T cells rebounded above baseline 24 hours after HC infusion, while NK cell numbers remained stable. Whole transcriptome profiling revealed down regulation of NF-κB signaling, apoptosis, and cell death signaling transcripts that preceded lymphocyte population changes, with activation of NK cell and glucocorticoid receptor signaling transcripts. Our study is the first to systematically characterize the effects of corticosteroids on the human immunome, and we demonstrate that HC exerts differential effects on B and T lymphocytes and natural killer cells in humans.
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.|Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, 20892, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Olnes
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kotliarov
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Angélique
authors.initials: A
authors.lastname: Biancotto
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Foo
authors.initials: F
authors.lastname: Cheung
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Jinguo
authors.initials: J
authors.lastname: Chen
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Rongye
authors.initials: R
authors.lastname: Shi
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Huizhi
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.|Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Tsang
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.|Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD, 20892, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Nussenblatt
mesh_terms: D000328:Adult; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D016130:Immunophenotyping; D007262:Infusions, Intravenous; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D006854:Hydrocortisone