Bacterial endotoxin induces biphasic changes in plasma ghrelin in healthy humans

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 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. Design and Setting: We conducted a randomized, placebo-controlled, crossover clinical trial at a university medical center. Study Participants: Participants included 10 healthy men. Intervention: After an overnight fast, study subjects were randomized to 2 ng/kg Escherichia coli endotoxin [lipopolysaccharide (LPS)] or placebo and monitored for 6 h. Main Outcome Measures: 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.