Context: 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 anti-inflammatory activities. Ghrelin is recently implicated in the host response to bacterial endotoxin in rodents and suggested as a possible therapeutical tool in sepsis.

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

Design: Randomized, placebo-controlled, cross-over clinical trial.

Setting: University Medical Center

Study Participants: 10 healthy men

Intervention: After an overnight fast, study subjects were randomized to 2ng/kg E. Coli endotoxin (lipoolysaccharide, LPS) or placebo, and monitored for 6 hours.

Main Outcome Measures: Ghrelin, GH, ACTH, cortisol, glucose, FFA, TNF-, IL-6, IL-1RA

Results: LPS administration induced a rapid ghrelin surge at 120 min ( ghrelin 100.2 ± 30.3 vs 7.2 ± 26.4 pg/ml in the placebo day, P=0.042). This ghrelin peak occurred 30 minutes after the TNF- peak and corresponded with IL-6, GH and ACTH peaks. Starting from 120 min and thereafter, ghrelin continuously decreased reaching a nadir at 5 hours after LPS administration ( ghrelin - 43.8 ± 28.4 compared to 70.3 ± 38.2 pg/ml in 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-neuro-endocrine mechanisms activated by systemic infection and inflammation in humans.