Effects of Systemically Administered Hydrocortisone on the Human Immunome

• DOI: 10.1038/srep23002
• Publication Date: 2016-03-14T10:24:19Z
• Authors: Matthew J. Olnes; Yuri Kotliarov; Angélique Biancotto; Foo Cheung; Jinguo Chen; Rongye Shi; Huizhi Zhou; Ena Wang; John S. Tsang; Robert Nussenblatt; ; Howard B. Dickler; Christopher S. Ho...; Francesco M. Mari...; J. Phillip McCoy; Shira Perl; Paula Schum; Pamela L. Schwart...; Giorgio Trinchieri; Janet Valdez; Neal S. Young
• Keywords: Adult; Male; 0303 health sciences; Time Factors; Dose-Response Relationship, Drug; Hydrocortisone; Gene Expression Profiling; B-Lymphocyte Subsets; Middle Aged; Flow Cytometry; Article; Lymphocyte Subsets; Immunophenotyping; 3. Good health; Killer Cells, Natural; 03 medical and health sciences; T-Lymphocyte Subsets; Cluster Analysis; Humans; Female; Lymphocyte Count; Infusions, Intravenous; Transcriptome; Signal Transduction

AbstractCorticosteroids 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.