Effects of coupled dose and rhythm manipulation of plasma cortisol levels on leukocyte transcriptional response to endotoxin challenge in humans.
Severe traumas are associated with hypercortisolemia due to both disruption of cortisol secretion rhythm and increase in its total concentration. Understanding the effects of altered cortisol levels and rhythms on immune function is of great clinical interest, to prevent conditions such as sepsis from complicating the recovery. This in vivo study assesses the responses of circulating leukocytes to coupled dose and rhythm manipulation of cortisol, preceding an immune challenge induced by endotoxin administration. Through continuous infusion, plasma cortisol concentration was increased to and kept constant at a level associated with major physiologic stress. In response, transcriptional programming of leukocytes was altered to display a priming response before endotoxin exposure. Enhanced expression of a number of receptors and signaling proteins, as well as lowered protein translation and mitochondrial function indicated a sensitization against potential infectious threats. Despite these changes, response to endotoxin followed very similar patterns in both cortisol and saline pre-treated groups except one cluster including probe sets associated with major players regulating inflammatory response. In sum, altered dose and rhythm of plasma cortisol levels engendered priming of circulating leukocytes when preceded an immune challenge. This transcriptional program change associated with stimulated surveillance function and suppressed energy-intensive processes, emphasized permissive actions of cortisol on immune function.
Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Kubra
K
Kamisoglu
Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Kirsten
K
Sleight
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Tung T
TT
Nguyen
Department of Surgery, Rutgers, Robert Wood Johnson Medical School, Clinical Academic Building, New Brunswick, NJ, USA.
Steve E
SE
Calvano
Department of Surgery, Rutgers, Robert Wood Johnson Medical School, Clinical Academic Building, New Brunswick, NJ, USA.
Susette M
SM
Coyle
Department of Surgery, Rutgers, Robert Wood Johnson Medical School, Clinical Academic Building, New Brunswick, NJ, USA.
Siobhan A
SA
Corbett
Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA Department of Surgery, Rutgers, Robert Wood Johnson Medical School, Clinical Academic Building, New Brunswick, NJ, USA yannis@rci.rutgers.edu.
Ioannis P
IP
Androulakis
D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D046228:Microarray Analysis; D011401:Promoter Regions, Genetic / Q000187:drug effects; D055815:Young Adult
D004731:Endotoxins; D008070:Lipopolysaccharides; D006854:Hydrocortisone
Cortisol; endotoxin; gene expression; leukocytes; systems biology