Influence of hypercortisolemia on the acute-phase protein response to endotoxin in humans.
BACKGROUND
The response to systemic infection includes the coordinated appearance of hepatic acute-phase proteins, the production of which may be influenced by a counterregulatory hormonal background. This study sought to assess the potential for hypercortisolemic conditions to influence fibrinogen kinetics and other acute-phase protein responses in humans with endotoxemia.


METHODS
Eleven hospitalized healthy male volunteers underwent two separate determinations of fibrinogen kinetics, one baseline and one after administration of endotoxin (2 ng/kg intravenously; lot EC-5). Seven volunteers were studied without hormonal manipulation and four in the presence of a hypercortisolemic background (hydrocortisone infusion, 3 micrograms/kg/min). Fibrinogen fractional synthetic rates were estimated from the incorporation of orally administered 15N-glycine, and fibrinogen, C-reactive protein, cortisol, tumor necrosis factor-alpha, and interleukin-6 levels were also determined.


RESULTS
The presence of an antecedent hypercortisolemic background resulted in an attenuated interleukin-6 response, as well as decreased fibrinogen synthesis and C-reactive protein appearance.


CONCLUSIONS
The current data suggest that glucocorticoid hormonal influences are of importance in the regulation of endotoxin-induced cytokine and acute-phase protein responses.
Rock
C S
CS
Department of Surgery, New York Hospital-Cornell University Medical College, NY 10021.
Coyle
S M
SM
Keogh
C V
CV
Lazarus
D D
DD
Hawes
A S
AS
Leskiw
M
M
Moldawer
L L
LL
Stein
T P
TP
Lowry
S F
SF
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000209:Acute-Phase Proteins; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen; D002097:C-Reactive Protein; D006854:Hydrocortisone