Ghrelin as an Acute-phase Reactant during Postoperative Stress Response

Abstract

Ghrelin is a growth hormone-releasing peptide, discovered in 1999 by Kojima et al. Its potential role in inflammation and stress response is not yet clear. The purpose of this study was to characterize perioperative levels of circulating ghrelin in relation to different surgical procedures. The authors compared plasma ghrelin changes with cortisol, cytokines, and acute-phase proteins. The prospective study was performed on 22 patients with resection for colon cancer (group 1). Group 2, functioning as a comparative group, consisted of 22 patients with elective laparotomic cholecystectomy. Plasma concentrations of ghrelin, cortisol, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, IL-6, IL-8, soluble IL-2 receptor, C reactive protein, and alpha1-antitrypsin were estimated repeatedly during a 72-hour postoperative period. Data revealed significant elevation of plasma ghrelin 24 hours after resection of coli (median 508.0 ng/l, interquartile range 398.2-633.7 ng/l) in relation to both preoperative levels (317.6 ng/l, 253.4-355.1 ng/l, p<0.01) and group 2 maximal postoperative levels (386.2 ng/l, 324-432 ng/l, p<0.05). Ghrelin levels returned to initial status 36-48 hours after surgery with subsequent decline to subnormal levels. The regression coefficient was the highest for ghrelin and TNF-alpha 24 hours after laparotomy (r=0.64, p<0.05) and for ghrelin and IL-6 24 hours after surgery (r=0.56, p<0.05). Maximal postoperative levels of all tested parameters except for cortisol and IL-1beta differed significantly between both patient groups at p<0.05. After large abdominal surgery, ghrelin shows itself as an acute-phase reactant. The significant correlation between ghrelin and inflammatory cytokines supposes their regulatory role in this period. Our comparison of more- and less-invasive surgical procedures with similar nutritional restrictions argues for a dominant role of inflammatory factors in postoperative ghrelin elevation.

Integrating GHS into the Ghrelin System

“…For example, ghrelin concentrations rise acutely after major surgery along with inflammatory cytokines like tumor-necrosis factor-alpha and interleukin (IL)-6 [569]. In mice, transgenic knockdown of the ghrelin receptor accentuates adverse effects of chronic social-defeat stress [570].…”

Effect of DA-9701, a Novel Prokinetic Agent, on Post-operative Ileus in Rats

“…Previous studies have revealed that circulating ghrelin levels, especially acyl ghrelin levels, fall in response to abdominal surgery and that the levels gradually recover over 24 hours. [22][23][24][25] We also found that ghrelin levels followed this pattern. However, our results were more complex and difficult to interpret.…”

“…[18][19][20][21] Circulating ghrelin levels, especially active ghrelin levels, decrease under conditions of abdominal surgery 22,23 and gradually normalize over 24 hours. 22,24,25 Therefore, the decrease of ghrelin after surgery could be a key driver of POI. Therapeutic effects of ghrelin and ghrelin receptor agonists have been shown on surgeryinduced POI.…”

Ghrelin – A Pleiotropic Hormone Secreted from Endocrine X/A-Like Cells of the Stomach

“…This decrease was accompanied by a delay of gastric emptying and a reduction of food intake (Stengel et al, 2011a). Interestingly, in humans an increase of total ghrelin was observed at 24 h post surgery compared to preoperative levels (Maruna et al, 2008), a difference that remains to be further investigated.…”