Bacterial Endotoxin Induces Biphasic Changes in Plasma Ghrelin in Healthy Humans

Abstract

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, placebocontrolled, 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-␣, IL-6, and IL-1 receptor antagonist.Results: LPS administration induced a rapid ghrelin surge at 120 min (⌬ ghrelin 100.2 Ϯ 30.3 vs. 7.2 Ϯ 26.4 pg/ml on the placebo day, P ϭ 0.042). This ghrelin peak occurred 30 min 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 h after LPS administration (⌬ ghrelin, Ϫ43.8 Ϯ 28.4 compared with 70.3 Ϯ 38.2 pg/ml on the control days, P ϭ 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.

Systemic administration of oxytocin reduces basal and lipopolysaccharide-induced ghrelin levels in healthy men

“…In accordance with previous findings (Cummings et al 2001, Vila et al 2007, plasma ghrelin increased during fasting (placebo sessions) and changed biphasically after LPS administration with a rapid surge at 2 h followed by a continuous decline afterwards (P!0 . 001; Fig.…”

“…Both OXT and ghrelin increase in the presence of several acute stressors (Van de Kar & Blair 1999, Vila et al 2007, Lutter et al 2008 and their administration alleviates the stress response (Dixit et al 2004, Lutter et al 2008. Ghrelin is thought to increase glucose availability to insulinindependent tissues such as the brain (Vestergaard et al 2008).…”

“…Both increase in response to stressors (Van de Kar & Blair 1999, Vila et al 2007, Lutter et al 2008, thereby exerting anti-inflammatory and anxiolytic effects (Dixit et al 2004, Landgraf & Neumann 2004, Lutter et al 2008. These peptides have opposing effects on appetite regulation, OXT being an anorexigenic hormone, while ghrelin an orexigenic one (Landgraf & Neumann 2004, van der Lely et al 2004.…”

Ghrelin Gene Products in Acute and Chronic Inflammation

“…In surgical patients with postoperative intraabdominal sepsis plasma levels of ghrelin increased and positively correlated with TNF-a and IL-6 levels (Maruna et al 2005). In healthy human subjects, LPS administration induced a biphasic change in circulating ghrelin levels, with a rapid increase reaching the maximum after the pick of TNF-a and a subsequent decrease with the nadir 5 h after LPS administration (Vila et al 2007). In rodent models of sepsis, induced either by LPS injection or caecal ligation and perforation, ghrelin treatment reduced the level of pro-inflammatory cytokines both in circulation and in tissues impacted by sepsis, such as lung and kidney (Peng et al 2012;Wang et al 2009;Wu et al 2007b).…”

Ghrelin in gastrointestinal diseases and disorders: A possible role in the pathophysiology and clinical implications (Review)

“…Plasma ghrelin levels were reported to increase rapidly in response to E. coli endotoxin (33). On the other hand, ghrelin levels were found to fall in a state of acute inflammation brought about by injection of bacterial lipopolysaccarides (34).…”