Pretreatment with stress cortisol enhances the human systemic inflammatory response to bacterial endotoxin
Mark P Yeager, Athos J Rassias, Patricia A Pioli, Michael L Beach, Kathleen Wardwell, Jane E Collins, Hong-Kee Lee, Paul M Guyre, Mark P Yeager, Athos J Rassias, Patricia A Pioli, Michael L Beach, Kathleen Wardwell, Jane E Collins, Hong-Kee Lee, Paul M Guyre
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 main 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.
Trial registration: ClinicalTrials.gov NCT00396344.
Conflict of interest statement
The authors have not disclosed any potential conflicts of interest.
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Source: PubMed