Abstract # 3118 Acylated ghrelin’s anti-inflammatory actions on lipopolysaccharide (LPS)-induced cytokine release

Abstract

Ghrelin regulates hypothalamic-pituitary-adrenal (HPA) axis responses to psychological stress at the brain and pituitary. Ghrelin is also a potent anti-inflammatory agent. However, its role in the HPA axis response to immune challenge is still imprecisely described. We hypothesized ghrelin’s anti-inflammatory actions on lipopolysaccharide (LPS)-induced cytokine release are mediated by activation of the HPA axis. We gave Wistar rats acylated ghrelin (AG; 1 mg/kg sc), concomitantly with lipopolysaccharide (LPS; E. coli, 100 μ g/kg i.p.) or pyrogen-free saline. We then assessed circulating cytokines and paraventricular nucleus of the hypothalamus (PVN) neuronal activation (c-Fos) as well as glucocorticoid and adrenocorticotropic hormone (ACTH) profiles. Our data show that AG markedly suppresses the circulating cytokine response to LPS, particularly that of tumour necrosis factor alpha, interleukin 1 and interleukin 10. In vitro, high AG can stimulate release of ACTH from the anterior pituitary, but in vivo the ACTH and glucocorticoid responses to LPS are not influenced by AG. AG alone activates the medial parvocellular region of the PVN, but it does not alter the LPS-induced activation of this region. These data suggest that AG markedly suppresses the circulating cytokine response to LPS but probably does not do this by modulating the HPA axis response in vivo.