Clin Chem Lab Med 2015; 53(11): 1815–1824 *Corresponding author: Tania Siahanidou, Neonatal Unit, First Department of Pediatrics, Athens University Medical School, “Aghia Sophia” Children’s Hospital, 115 27 Athens, Greece, Phone: +30 213 2013889, Fax: +30 210 7473121, E-mail: siahan@med.uoa.gr Alexandra Margeli, Eugenia Hantzi and Ioannis Papassotiriou: Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, Athens, Greece Chrysanthi Tsirogianni and George Chrousos: Neonatal Unit, First Department of Pediatrics, Athens University Medical School, Athens, Greece Tania Siahanidou*, Alexandra Margeli, Chrysanthi Tsirogianni, Eugenia Hantzi, Ioannis Papassotiriou and George Chrousos Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates with infection DOI 10.1515/cclm-2014-1250 Received December 16, 2014; accepted March 11, 2015; previously published online April 14, 2015 Abstract Background: Early diagnosis and treatment of neonatal infection is important to prevent morbidity and mortal- ity. The gastrointestinal tract-derived hormones ghrelin and peptide YY (PYY), which participate in the regulation of food intake and energy balance, may also play roles in the inflammatory response. Their involvement in neonatal infection is not known. Methods: Plasma ghrelin and PYY(3-36) levels were seri- ally measured (by ELISA) on Days 0, 1, 2, 3 and 7 following admission in 36-term neonates with febrile infection (22 of them were septic) and once in 20 healthy term neonates of similar postnatal age and gender distribution, as controls. Associations of ghrelin and PYY(3-36) levels with clini- cal and laboratory parameters, including anthropomet- rics, fever, leukocyte and platelet counts, serum glucose, C-reactive protein (CRP) and serum amyloid A levels, were assessed. Results: Plasma ghrelin levels were significantly higher in infected neonates than in controls at each study day (p = 0.009), whereas PYY(3-36) levels did not differ sig- nificantly between patients and controls at any day. In infected neonates, ghrelin levels on admission correlated negatively with serum glucose levels (p = 0.003), whereas fever change during the course of infection was signifi- cantly associated with change of ghrelin levels (p = 0.01). Receiver operating characteristic analysis of ghrelin levels resulted in significant areas under the curve (AUC) for detecting infected neonates on admission (AUC = 0.728, p = 0.005). Conclusions: Circulating ghrelin, but not PYY(3-36), levels are increased in neonates with infection, possibly reflect- ing and/or participating in the inflammatory process. Keywords: biomarker; fever; ghrelin; infection; peptide YY; sepsis. Introduction Infections remain one of the leading causes of morbidity and mortality in neonatal age and may also have severe long-term consequences [1]. Infants who have suffered neonatal sepsis face an increased risk for brain damage and neurodevelopmental delays [2, 3], whereas, experi- mental data have shown that inflammation/infection early in life may alter the developmental trajectory of the immune system and the brain [4, 5]. Early diagnosis and management of neonatal infection improves prog- nosis; thus, the identification of new or complementary biomarkers of neonatal infection or sepsis is of potential importance [6]. Ghrelin and peptide YY (PYY) (3-36), one of the two major molecular forms of total PYY – the other isoform being PYY(1-36)-, are gastrointestinal tract-derived hor- mones that play roles in the regulation of food intake and energy balance with opposite effects; ghrelin is orexigenic, whereas PYY(3-36) suppresses food intake [7, 8]. Furthermore, studies in animals and human adults have clearly shown that ghrelin has additional proper- ties; among others, ghrelin is implicated in systemic inflammation [9]. Circulating ghrelin is one of the first hormones that rapidly increase in the human adult physi- ological response to bacterial endotoxin [10]. Interest- ingly, ghrelin administration has beneficial effects in septic animal models. Treatment with ghrelin decreased proinflammatory cytokines and gut-derived norepineph- rine release [11, 12], improved organ blood flow by inhib- iting nuclear factor-κ B [13], corrected, at least partially, Brought to you by | Universita degli Studi di Padova Authenticated Download Date | 3/28/16 3:29 AM