Ghrelin and Leptin Elevation in Postoperative Intra-Abdominal Sepsis

Abstract

Background: Both ghrelin and leptin are important signals in the regulation of food intake and energy balance. Leptin concentrations are elevated in the majority of obese individuals, and its levels usually correlate with adiposity and body mass index. Ghrelin as a new growth hormone (GH)-releasing peptide was discovered in 1999. Ghrelin stimulates food intake and exhibits gastroprotective properties. Many other regulatory effects of both ghrelin and leptin involving cardiovascular, gastrointestinal, renal, and endocrine systems were revealed. New experimental studies show both hormones as new acute phase reactants in animal models of inflammatory reaction. The aim of this study was to characterize the levels of circulating ghrelin and leptin in relation to systemic inflammatory response. We used a postoperative bacterial sepsis after large abdominal surgery as a model of cytokine network hyperstimulation. Patients and Methods:The prospective study was performed on 25 surgical patients with proven postoperative intra-abdominal sepsis after large abdominal surgery. Plasma levels of ghrelin (RIA), leptin, TNF-α, IL-1β, sIL-2R, IL-6 (ELISA analysis), CRP and α₁-antitrypsin (nephelometric analysis) were analyzed. Results: Authors demonstrate statistically significant elevation of plasma ghrelin (492.3 ± 70.6 ng/l) and leptin (31.6 ± 12.2 µg/l) compared with the control group (336.5 ± 46,1, p < 0.01 for ghrelin, 3.5 ± 1.2 µg/l, p < 0.001 for leptin). The regression coefficient was the highest for ghrelin and IL-6 (r = 0,44, p < 0.05), and for ghrelin and TNF (r = 0.43, p < 0.05) in the sepsis group. In regard to leptin, the regression coefficient was the highest for IL-6 and leptin (r = 0.53, p < 0.05) and for leptin and CRP (r = 0.51, p < 0.05). There was no significant correlation between ghrelin and IL-1β, ghrelin and sIL-2R, and leptin and IL-1β. Conclusions: During postoperative intra-abdominal sepsis, both ghrelin and leptin plasma levels are elevated and positively correlate with both inflammatory cytokines (TNF-α, IL-6) and main APP member (CRP). It supports experimental finding that TNF-α and IL-6 can be important regulatory factors of their synthesis. This hormonal reaction is not specific to sepsis – the significant increase of both ghrelin and leptin occurs during an uncomplicated postoperative response, although in a lesser extent than was shown in sepsis.

Bacterial Endotoxin Induces Biphasic Changes in Plasma Ghrelin in Healthy Humans

“…The response of ghrelin Ϫ/Ϫ mice to endotoxin would answer the question whether ghrelin is a key regulator or just a by-player in the complicated immuno-neuroendocrine mechanisms. Ghrelin was found to be significantly elevated in 25 surgical patients with postoperative intraabdominal sepsis (32), but more studies and a better profiling of ghrelin fluctuations in acute infections are needed before testing its possible therapeutic effect in humans.…”

Expression, regulation and biological actions of growth hormone (GH) and ghrelin in the immune system

“…Patients with ankylosing spondylitis that is characterized by a chronic inflammation of the spine [130], and septic patients were reported to have high serum concentrations of ghrelin [131]. The increase in serum ghrelin was also reported in animal models: serum ghrelin concentrations were higher in rats with cerulein-induced severe pancreatitis [132] and those with adjuvant-induced arthritis [133], and in mice with trinitrobenzene sulfate-induced acute colitis [134].…”

Ghrelin Gene Products in Acute and Chronic Inflammation

“…Several studies, both in animal models and humans, have demonstrated that sepsis modulates plasmatic ghrelin concentrations and that the administration of ghrelin has beneficial effects on sepsis. 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).…”