Pretreatment with stress cortisol enhances the human systemic inflammatory response to bacterial endotoxin.
Crit Care Med
; 37(10): 2727-32, 2009 Oct.
Article
en En
| MEDLINE
| ID: mdl-19885996
ABSTRACT
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.DESIGN:
Prospective, randomized, double-blind, placebo-controlled clinical investigation.SETTING:
Academic medical center.SUBJECTS:
Thirty-six healthy human volunteers.INTERVENTIONS:
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. MEASUREMENTS AND MAINRESULTS:
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteína C-Reactiva
/
Hidrocortisona
/
Citocinas
/
Hormona Adrenocorticotrópica
/
Síndrome de Respuesta Inflamatoria Sistémica
/
Endotoxinas
/
Escherichia coli
/
Recuento de Leucocitos
/
Antiinflamatorios
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Crit Care Med
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos