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We used large collections of public blood transcriptomic datasets and different GC-induced query genes to obtain 2 robust gene expression correlation signatures of GC induction, either in the absence or in the presence of severe inflammation. GC signature 1 originated from circadian cortisol with biases for gene expression in natural killer cells and neutrophils. GC signature 2 originated from GC in severe inflammation, mainly with biases for gene expression in monocytes and neutrophils. Many genes upregulated by GC treatment in septic shock and burn shock were also present as high-ranking genes in GC signatures, which pointed to their direct regulation by GC. Robust GC signatures were also obtained from dataset collections of different tissues for comparison, and of monocytes and neutrophils, separately. Gene induction by GC was put into a wider framework of gene expression in circulating monocytes and neutrophils in health and during systemic inflammation, which included macrophage-like cells and a hypoxia-related gene expression signature in monocytes in severe inflammation. We present and interpret a large number of GC-regulated genes in different blood cells and tissues in vivo and select 2 whole blood transcriptomic biomarker gene sets, GC-1 and GC-2, for monitoring cortisol action in health and in severe inflammation, respectively.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag068","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:50:02Z","timestamp":1780487402000},"source":"Crossref","is-referenced-by-count":0,"title":["Glucocorticoid-driven gene expression in circulating monocytes and neutrophils in health and severe inflammation"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8833-8699","authenticated-orcid":false,"given":"Arthur","family":"Molendijk","sequence":"first","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100 , Utrecht 3584 CX ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5636-6453","authenticated-orcid":false,"given":"Leo","family":"Koenderman","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Center for Translational Immunology, University Medical Center , Utrecht University, Heidelberglaan 100, Utrecht 3584 CX ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"2026062905115493900_qiag068-B1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1210\/er.2015-1080","article-title":"The functional and clinical significance of the 24-hour rhythm of circulating glucocorticoids","volume":"38","author":"Oster","year":"2017","journal-title":"Endocr 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