title: Glucocorticoids enhance the in vivo migratory response of human monocytes.
abstract: Glucocorticoids (GCs) are best known for their potent anti-inflammatory effects. However, an emerging model for glucocorticoid (GC) regulation of in vivo inflammation also includes a delayed, preparatory effect that manifests as enhanced inflammation following exposure to an inflammatory stimulus. When GCs are transiently elevated in vivo following exposure to a stressful event, this model proposes that a subsequent period of increased inflammatory responsiveness is adaptive because it enhances resistance to a subsequent stressor. In the present study, we examined the migratory response of human monocytes/macrophages following transient in vivo exposure to stress-associated concentrations of cortisol. Participants were administered cortisol for 6h to elevate in vivo cortisol levels to approximate those observed during major systemic stress. Monocytes in peripheral blood and macrophages in sterile inflammatory tissue (skin blisters) were studied before and after exposure to cortisol or placebo. We found that exposure to cortisol induced transient upregulation of monocyte mRNA for CCR2, the receptor for monocyte chemotactic protein-1 (MCP-1/CCL2) as well as for the chemokine receptor CX3CR1. At the same time, mRNA for the transcription factor IκBα was decreased. Monocyte surface expression of CCR2 but not CX3CR1 increased in the first 24h after cortisol exposure. Transient exposure to cortisol also led to an increased number of macrophages and neutrophils in fluid derived from a sterile inflammatory site in vivo. These findings suggest that the delayed, pro-inflammatory effects of cortisol on the human inflammatory responses may include enhanced localization of effector cells at sites of in vivo inflammation.
authors.affiliation: Department of Anesthesiology, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03755, USA. Electronic address: mark.p.yeager@hitchcock.org.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Yeager
authors.affiliation: Department of Obstetrics and Gynecology, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03755, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Pioli
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, 1 Medical Center Drive, Lebanon, NH 03755, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Collins
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, 1 Medical Center Drive, Lebanon, NH 03755, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Barr
authors.affiliation: Department of Anesthesiology, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03755, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Metzler
authors.affiliation: Department of Anesthesiology, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03755, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Sites
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, 1 Medical Center Drive, Lebanon, NH 03755, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Guyre
mesh_terms: D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D018932:Chemokine CCL2 / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D008297:Male; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2 / Q000096:biosynthesis / Q000276:immunology; D013312:Stress, Physiological; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D012333:RNA, Messenger; D054390:Receptors, CCR2; D006854:Hydrocortisone
keywords: CCR2; CX3CR1; Cortisol; IκBα; Macrophage; Monocyte; Stress