Bacterial endotoxin induces biphasic changes in plasma ghrelin in healthy humans.
BACKGROUND
Ghrelin is a gut hormone with a highly preserved biological activity, which seems not to be restricted to the regulation of food intake, body composition, and growth. Continuous research is unraveling new properties of ghrelin, among others cardiovascular and antiinflammatory activities. Ghrelin is recently implicated in the host response to bacterial endotoxin in rodents and suggested as a possible therapeutic tool in sepsis.


OBJECTIVE
This study aimed to investigate plasma ghrelin levels during human bacterial endotoxemia.


METHODS
We conducted a randomized, placebocontrolled, crossover clinical trial at a university medical center.


METHODS
Participants included 10 healthy men.


METHODS
After an overnight fast, study subjects were randomized to 2 ng/kg Escherichia coli endotoxin [lipopolysaccharide (LPS)] or placebo and monitored for 6 h.


METHODS
We measured ghrelin, GH, ACTH, cortisol, glucose, free fatty acids, TNF-alpha, IL-6, and IL-1 receptor antagonist.


RESULTS
LPS administration induced a rapid ghrelin surge at 120 min (Delta ghrelin 100.2 +/- 30.3 vs. 7.2 +/- 26.4 pg/ml on the placebo day, P = 0.042). This ghrelin peak occurred 30 min after the TNF-alpha peak and corresponded with IL-6, GH, and ACTH peaks. Starting from 120 min and thereafter, ghrelin continuously decreased, reaching a nadir at 5 h after LPS administration (Delta ghrelin, -43.8 +/- 28.4 compared with 70.3 +/- 38.2 pg/ml on the control days, P = 0.038).


CONCLUSIONS
Ghrelin is one of the first hormones rapidly increasing in the human physiological response to bacterial endotoxic shock. Plasma ghrelin might be part of the complex immuno-neuroendocrine mechanisms activated by systemic infection and inflammation in humans.
Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, A-1090, Vienna, Austria.
Greisa
G
Vila
Christina
C
Maier
Michaela
M
Riedl
Peter
P
Nowotny
Bernhard
B
Ludvik
Anton
A
Luger
Martin
M
Clodi
D000328:Adult; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D009490:Neurosecretory Systems / Q000502:physiology; D018805:Sepsis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D054439:Ghrelin; D008070:Lipopolysaccharides