Pretreatment with stress cortisol enhances the human systemic  inflammatory response to bacterial endotoxin.
OBJECTIVE
There is continuing controversy regarding the effect of glucocorticoids on a systemic inflammatory process. Based ona model of glucocorticoid action that includes both pro- and anti-inflammatory effects, we used the human experimental endotoxemia model to test the hypothesis that a transient elevation of plasma cortisol to stress-associated levels would enhance a subsequent (delayed) systemic inflammatory response to bacterial endotoxin.


METHODS
Prospective, randomized, double-blind, placebo-controlled clinical investigation.


METHODS
Academic medical center.


METHODS
Thirty-six healthy human volunteers.


METHODS
Participants were randomized to receive a 6-hr intravenous infusion of saline (control), an intermediate dose of cortisol (Cort80; 6.3 mg/hr/70 kg), or a high dose of cortisol (Cort160; 12.6 mg/hr/70 kg) on day 1. On day 2, participants received an intravenous injection of 2 ng/kg Escherichia coli endotoxin followed by serial measurements of plasma cytokine concentrations.


RESULTS
Baseline participant characteristics and cortisol and cytokine concentrations were similar in all three groups. The plasma cortisol response to endotoxemia on day 2 was similar in all three groups. The interleukin-6 response to endotoxemia was significantly increased in the Cort80 Group compared with the control Group (p = .004), whereas the interleukin-10 response was significantly suppressed (p = .034). Corresponding results for the Cort160 Group were not significantly different from control Group values.


CONCLUSIONS
In this study, transient elevation of in vivo cortisol concentrations to levels that are observed during major systemic stress enhanced a subsequent, delayed in vivo inflammatory response to endotoxin. This appeared to be a dose-dependent effect that was more prominent at intermediate concentrations of cortisol than at higher concentrations of cortisol.
Yeager
Mark P
MP
Department of Anesthesiology and Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. Mark.P.Yeager@Hitchcock.Org
Rassias
Athos J
AJ
Pioli
Patricia A
PA
Beach
Michael L
ML
Wardwell
Kathleen
K
Collins
Jane E
JE
Lee
Hong-Kee
HK
Guyre
Paul M
PM
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000378:metabolism*; D016207:Cytokines / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology; D007262:Infusions, Intravenous; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011292:Premedication; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D016753:Interleukin-10; D000324:Adrenocorticotropic Hormone; D002097:C-Reactive Protein; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone