Role of Ghrelin on Growth Hormone/insulin-like Growth Factor-1 Axis During Endotoxemia

Objective: To investigate the anti-inflammatory property of ghrelin treatment on the Growth Hormone (GH)/Insulin-like Growth Factor-I (IGF-1) axis in Wistar rats that have undergone endotoxemia.

Design: In this randomized animal study, lipopolysaccharide (LPS) (5 mg/kg; intraperitoneal) was administered to induce endotoxemia, and ghrelin (15 nmol/kg; endovenous) was injected simultaneously. Blood and liver samples were collected 2 h, 6 h and 12 h after LPS administration for analysis.

Measurements: Tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, beta (IL-1β), and IL-6 from both blood and liver were determined by ELISA assay. Serum nitrate was determined by chemiluminescense. Growth hormone receptor (GHR) and growth hormone secretagogue receptor 1a (GHSR-1a) were determined by western blotting. GHR mRNA and IGF-1 mRNA were determined by RT-PCR.

Results: LPS administration induced a decrease in IGF-1 and GH serum levels, characterizing GH/IGF-1 axis disruption. Ghrelin treatment attenuated the decrease of serum levels of IGF-1 as well as the increase of TNF-α, IL-1β, IL-6 and nitrate induced by LPS. The increase of induced GHSR-1a protein expression seen in the LPS group after 2 h remained until 6 h after ghrelin treatment. However, attenuation of the circulating IGF-1 decrease by ghrelin treatment was not accompanied by changes in GHR protein expression nor GHR and IGF-1 gene expression.

Conclusion: Ghrelin was able to attenuate changes in the GH/IGF-1 axis observed during systemic inflammation, which may be due to the modulation of pro-inflammatory mediators release.