Role of Ghrelin on Growth Hormone (GH) – Insuline like Growth Factor-1 (IGF-1) Axis during an Experimental Model of Sepsis

Presentation Number: SAT 433
Date of Presentation: April 1st, 2017

Evelin Capellari Carnio*, Felipe Faim and Luiz Guilherme Branco
University of Sao Paulo, Ribeirao Preto, Brazil

Abstract

Sepsis and its most deleterious complication, septic shock, represent the systemic inflammatory response to infection, which may microbiologically be classified as confirmed, probable or possible.  This pathophysiology condition induces changes in growth hormone (GH) / insulin-like growth factor-1 (IGF-1) axis. We observe an elevation in circulating GH levels and we also expected an elevation in IGF-1 levels, once GH is able to induce the synthesis of IGF-1. However the increase in GH was accompanied by a decrease of IGF-1, which may suggest a resistance to GH, resulting in changes on GH / IGF-1 axis. Among the possible causes for this resistance, strong evidence points to the involvement of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL) -1β and IL-6.

Ghrelin is a hormone, which is known for its ability to release GH, and has an orexigenic effect. In addition, several studies have shown the anti-inflammatory properties of this hormone. It has also been demonstrated that it is able to attenuate the increase in pro-inflammatory cytokines such as TNF-α, IL1-β, nitric oxide and IL6.

The hypothesis of this study is that treatment with ghrelin may attenuate the change on GH/IGF-1 axis by reducing pro-inflammatory mediators as nitric oxide, tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β and IL-6 during sepsis model induced by lipopolissacharide (LPS) administration (5mg / kg, ip). To study the role of ghrelin (15nmol / kg iv) on GH / IGF-1 axis, we performed administration of LPS in male Wistar rats (number of animals per group: 6-10).

Results: Intraperitoneal LPS administration induced a decrease in IGF-1 (1752±8.2 vs. 1158±12.2 pg/ml; P=0.018) and GH serum levels (4980±32 vs. 528±42 pg/ml; P=0.042); characterizing the change of GH / IGF-1 axis. Intravenously treatment with ghrelin attenuated the decrease of serum levels of IGF-1 (278±23 vs. 680±42 pg/ml; P=0.0018); induced by LPS. LPS induced increase in serum nitrate and pro-inflammatory cytokines as TNF-α, IL1-β, IL6. In liver, LPS also led to increased cytokines TNF-α, IL1-β and IL6. Treatment with ghrelin attenuated the increase in pro-inflammatory mediators, nitrate, TNF-α, IL1-β and IL-6 induced by LPS administration in both blood and liver.

Conclusion: Treatment with ghrelin attenuated the decrease in serum levels of IGF-1 in septic animals, suggesting a possible improvement in hepatic GH insensitivity.

 

Nothing to Disclose: ECC, FF, LGB