Central ghrelin administration reduces starvation-induced inflammation in rats
Darko Stevanovic1, Vladimir Trajkovic2, Dejan Nesic1, Dragan Micic3, Mirjana Sumarac-Dumanovic3, Vera Popovic3 & Vesna Starcevic1
The aim of the study was to investigate the influence of intracerebroventricular (ICV) injections of ghrelin on secretion of pro-inflammatory (TNF, IL-1, IFN-γ) and anti-inflammatory cytokines (TGF-β) in starved rats. Male Wistar rats (4 weeks old, 12 per group) were fed ad libitum or starved by caloric restriction (40% of chow consumed by their ad libitum fed controls from previous day) for 4 weeks. Afterwards, half of the animals in each group received ICV injections of ghrelin in PBS (0.15 nmol in 5 μl of PBS, daily for 5 consecutive days) or PBS alone. Rats were sacrificed two hours after the last injection, their blood was collected and serum concentrations of cytokines, ACTH and corticosterone were measured by ELISA. The concentrations of the pro-inflammatory cytokines TNF, IL-1 and IFN-γ were significantly increased in starved compared to rats fed ad libitum (P<0.01), while the levels of the anti-inflammatory TGF-β did not significantly differ between the two groups (P>0.05). The ICV application of ghrelin significantly reduced the blood levels of all three pro-inflammatory cytokines (P<0.05), while not affecting those of TGF-β. The observed anti-inflammatory effect of ICV applied ghrelin in starved rats was accompanied by activation of the hypothalamopituitaryadrenal (HPA) axis, reflected in the increase in serum levels of both ACTH and corticosterone (P<0.05). These results indicate that central ghrelin application might suppress starvation-induced systemic inflammation through activation of HPA axis and subsequent release of the anti-inflammatory corticosterone.