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.
| Original language | English (US) |
|---|---|
| Article number | 23002 |
| Journal | Scientific Reports |
| Volume | 6 |
| DOIs | |
| State | Published - Mar 14 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- General
Cite this
Effects of Systemically Administered Hydrocortisone on the Human Immunome. / The CHI Consortium.
In: Scientific Reports, Vol. 6, 23002, 14.03.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of Systemically Administered Hydrocortisone on the Human Immunome
AU - The CHI Consortium
AU - Olnes, Matthew J.
AU - Kotliarov, Yuri
AU - Biancotto, Angélique
AU - Cheung, Foo
AU - Chen, Jinguo
AU - Shi, Rongye
AU - Zhou, Huizhi
AU - Wang, Ena
AU - Tsang, John S.
AU - Nussenblatt, Robert
AU - Dickler, Howard B.
AU - Hourigan, Christopher
AU - Marincola, Francesco M.
AU - McCoy, J. Phillip
AU - Perl, Shira
AU - Schum, Paula
AU - Schwartzberg, Pamela L.
AU - Trinchieri, Giorgio
AU - Valdez, Janet
AU - Young, Neal S.
PY - 2016/3/14
Y1 - 2016/3/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84961843560&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84961843560&partnerID=8YFLogxK
U2 - 10.1038/srep23002
DO - 10.1038/srep23002
M3 - Article
C2 - 26972611
AN - SCOPUS:84961843560
VL - 6
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 23002
ER -