Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates with infection
-
Tania Siahanidou
, Alexandra Margeli
, Chrysanthi Tsirogianni , Eugenia Hantzi , Ioannis Papassotiriou and George Chrousos
Abstract
Background: Early diagnosis and treatment of neonatal infection is important to prevent morbidity and mortality. 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 serially 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 clinical and laboratory parameters, including anthropometrics, 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 significantly 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 significantly 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 reflecting and/or participating in the inflammatory process.
Acknowledgments
This work was supported by Athens University.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Financial support: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am 2013;60:367–89.10.1016/j.pcl.2012.12.003Search in Google Scholar PubMed PubMed Central
2. Bakhuizen SE, de Haan TR, Teune MJ, van Wassenaer-Leemhuis AG, van der Heyden JL, van der Ham DP, et al. Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications. Acta Paediatr 2014;103:1211–8.10.1111/apa.12764Search in Google Scholar PubMed
3. Mitha A, Foix-L’Helias L, Arnaud C, Marret S, Vieux R, Aujard Y, et al. Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants. Pediatrics 2013;132:e372–80.10.1542/peds.2012-3979Search in Google Scholar PubMed
4. Bilbo SD. Frank A. Beach award: programming of neuroendocrine function by early-life experience: a critical role for the immune system. Horm Behav 2013;63:684–91.10.1016/j.yhbeh.2013.02.017Search in Google Scholar PubMed PubMed Central
5. Hagberg H, Gressens P, Mallard C. Inflammation during fetal and neonatal life: implications for neurologic and neuropsychiatric disease in children and adults. Ann Neurol 2012;71:444–57.10.1002/ana.22620Search in Google Scholar PubMed
6. Mussap M, Noto A, Cibecchini F, Fanos V. The importance of biomarkers in neonatology. Semin Fetal Neonat Med 2013;18:56–64.10.1016/j.siny.2012.10.006Search in Google Scholar PubMed
7. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, et al. Ghrelin enhances appetite and increase food intake in humans. J Clin Endocrinol Metab 2001;86:5992–5.10.1210/jcem.86.12.8111Search in Google Scholar PubMed
8. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 2002;418:650–4.10.1038/nature00887Search in Google Scholar PubMed
9. Stengel A, Tache Y. Ghrelin-a pleiotropic hormone secreted from endocrine x/a-like cells of the stomach. Front Neurosci 2012;6:24.10.3389/fnins.2012.00024Search in Google Scholar PubMed PubMed Central
10. Vila G, Maier C, Riedl M, Nowotny P, Ludvik B, Luger A, et al. Bacterial endotoxin induces biphasic changes in plasma ghrelin in healthy humans. J Clin Endocrinol Metab 2007;92:3930–4.10.1210/jc.2007-1194Search in Google Scholar PubMed
11. Wu R, Dong W, Cui X, Zhou M, Simms HH, Ravikumar TS, et al. Ghrelin down-regulates proinflammatory cytokines in sepsis through activation of the vagus nerve. Ann Surg 2007;245: 480–6.10.1097/01.sla.0000251614.42290.edSearch in Google Scholar
12. Jacob A, Rajan D, Pathickal B, Balouch I, Hartman A, Wu R, et al. The inhibitory effect of ghrelin on sepsis-induced inflammation is mediated by the MAPK phosphatase-1. Int J Mol Med 2010;25:159–64.Search in Google Scholar
13. Wu R, Dong W, Zhou M, Zhang F, Marini CP, Ravikumar TS, et al. Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats. Am J Respir Crit Care Med 2007;176:805–13.10.1164/rccm.200604-511OCSearch in Google Scholar
14. Das UN. Relationship between gut and sepsis: role of ghrelin. World J Diabetes 2011;15:1–7.10.4239/wjd.v2.i1.1Search in Google Scholar
15. Wu R, Chaung WW, Dong W, Ji L, Barrera R, Nicastro J, et al. Ghrelin maintains the cardiovascular stability in severe sepsis. J Surg Res 2012;178:370–7.10.1016/j.jss.2011.12.021Search in Google Scholar
16. Wu R, Dong W, Qiang X, Wang H, Blau SA, Ravikumar TS, et al. Orexigenic hormone ghrelin ameliorates gut barrier dysfunction in sepsis in rats. Crit Care Med 2009;37:2421–6.10.1097/CCM.0b013e3181a557a2Search in Google Scholar
17. Wang W, Bansal S, Falk S, Ljubanovic D, Schrier R. Ghrelin protects mice against endotoxemia-induced acute kidney injury. Am J Physiol Renal Physiol 2009;297:F1032–7.10.1152/ajprenal.00044.2009Search in Google Scholar
18. Chang L, Zhao J, Yang J, Zhang Z, Tang C. Therapeutic effects of ghrelin on endotoxic shock in rats. Eur J Pharmacol 2003;473:171–6.10.1016/S0014-2999(03)01972-1Search in Google Scholar
19. Zamir O, Hasselgren PO, Higasiguchi T, Frederick JA, Fischer JE. Effect of sepsis or cytokine administration on release of gut peptides. Am J Surg 1992;163:181–4.10.1016/0002-9610(92)90273-TSearch in Google Scholar
20. Higashiguchi T, Noguchi Y, Noffsinger A, Fischer JE, Hasselgren PO. Sepsis increases production of total secreted proteins, vasoactive intestinal peptide, and peptide YY in isolated rat enterocytes. Am J Surg 1994;168:251–6.10.1016/S0002-9610(05)80197-7Search in Google Scholar
21. Holler JP, Schmitz J, Roehrig R, Wilker S, Hecker A, Padberg W, et al. Expression of peptide YY by human blood leukocytes. Peptides 2014;58:78–82.10.1016/j.peptides.2014.05.009Search in Google Scholar PubMed
22. Chelikani PK, Haver AC, Reidelberger RD. Intravenous infusion of PYY(3-36) potently inhibits food intake in rats. Endocrinology 2005;146:879–88.10.1210/en.2004-1138Search in Google Scholar PubMed
23. Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005;6:2–8.10.1097/01.PCC.0000149131.72248.E6Search in Google Scholar PubMed
24. Hedegaard SS, Wisborg K, Hvas A. Diagnostic utility of biomarkers for neonatal sepsis – a systematic review. Infect Dis (Lond) 2015;47:117–24.10.3109/00365548.2014.971053Search in Google Scholar PubMed
25. Siahanidou T, Mandyla H, Militsi H, Papassotiriou I, Chrousos G. Peptide YY(3-36) represents a high percentage of total PYY immunoreactivity in preterm and full-term infants and correlates independently with markers of adiposity and serum ghrelin concentrations. Pediatr Res 2007;62:200–3.10.1203/PDR.0b013e3180a76dadSearch in Google Scholar PubMed
26. Yilmaz Z, Ilcol YO, Ulus IH. Endotoxin increases plasma leptin and ghrelin levels in dogs. Crit Care Med 2008;36:828–33.10.1097/01.CCM.0B013E3181611F5AASearch in Google Scholar PubMed
27. Koch A, Sanson E, Helm A, Voigt S, Trautwen C, Tacke F. Regulation and prognostic relevance of serum ghrelin concentrations in critical illness and sepsis. Crit Care 2010;14:R94.10.1186/cc9029Search in Google Scholar PubMed PubMed Central
28. Maruna P, Gurlich R, Frasko R, Rosicka M. Ghrelin and leptin elevation in postoperative intra-abdominal sepsis. Eur Surg Res 2005;37:354–9.10.1159/000090336Search in Google Scholar PubMed
29. Nematy M, O’Flynn JE, Wandrag L, Brynes AE, Brett SJ, Patterson M, et al. Changes in appetite related gut hormones in intensive care unit patients: a pilot cohort study. Crit Care 2006;10:R10.10.1186/cc3957Search in Google Scholar PubMed PubMed Central
30. Wang L, Basa NR, Shaikh A, Luckey A, Heber D, St-Pierre DH, et al. LPS inhibits fasted plasma ghrelin levels in rats: role of IL-1 and PGs and functional implications. Am J Physiol Gastrointest Liver Physiol 2006;291:G611–20.10.1152/ajpgi.00533.2005Search in Google Scholar PubMed
31. Siahanidou T, Mandyla H, Vounatsou M, Anagnostakis D, Papassotiriou I, Chrousos GP. Circulating YY concentrations are higher in preterm than full-term infants and correlate negatively with body weight and positively with serum ghrelin concentrations. Clin Chem 2005;51:2131–7.10.1373/clinchem.2005.054908Search in Google Scholar PubMed
32. Madison LD, Scarlett JM, Levasseur P, Zhu X, Newcomb K, Batra A, et al. Prostacyclin signaling regulates circulating ghrelin during acute inflammation. J Endocrinol 2008;196:263–73.10.1677/JOE-07-0478Search in Google Scholar PubMed
33. Iwakura H, Kangawa K, Nakao K. The regulation of circulating ghrelin-with recent updates from cell-based assays. Endocr J 2015;62:107–22.10.1507/endocrj.EJ14-0419Search in Google Scholar PubMed
34. Chabot F, Caron A, Laplante M, St-Pierre DH. Interrelationships between ghrelin, insulin and glucose homeostasis: physiological relevance. World J Diabetes 2014;5:328–41.10.4239/wjd.v5.i3.328Search in Google Scholar PubMed PubMed Central
35. Soriano RN, Nicoli LG, Carnio EC, Branco LG. Exogenous ghrelin attenuates endotoxin fever in rats. Peptides 2011;32:2372–6.10.1016/j.peptides.2011.02.019Search in Google Scholar PubMed
36. Stein M, Schachter-Davidov A, Babai I, Tasher D, Somekh E. The accuracy of C-reactive protein, procalcitonin, and s-TREM-1 in the prediction of serious bacterial infection in neonates. Clin Pediatr (Phila) [Epub ahead of print 2014 Oct 7].Search in Google Scholar
©2015 by De Gruyter
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- Frontmatter
- Editorials
- Laboratory medicine does matter in science (and medicine)… yet many seem to ignore it
- The standardization of the urine albumin assays: no longer deferrable
- Reviews
- The role of telomeres and vitamin D in cellular aging and age-related diseases
- Atypical hemolytic uremic syndrome: from diagnosis to treatment
- Clinical relevance and contemporary methods for counting blood cells in body fluids suspected of inflammatory disease
- EFLM Opinion Paper
- How to assess the quality of your analytical method?
- Genetics and Molecular Diagnostics
- Validation of CFTR intronic variants identified during cystic fibrosis population screening by a minigene splicing assay
- General Clinical Chemistry and Laboratory Medicine
- Uncertainty in measurement for 43 biochemistry, immunoassay, and hemostasis routine analytes evaluated by a method using only external quality assessment data
- A study examining the bias of albumin and albumin/creatinine ratio measurements in urine
- National survey on appropriateness of clinical biochemistry reporting in China
- Potentiometric measurement of urinary iodine concentration in patients with thyroid diseases with and without previous exposure to non-radioactive iodine
- Determination of 21-hydroxylase autoantibodies: inter-laboratory concordance in the Euradrenal International Serum Exchange Program
- Value of a commercial kit for detecting anti-C1q autoantibodies and correlation with immunological and clinical activity of lupus nephritis
- Comparison of the bead-based simultaneous analysis of specific platelet antibodies assay (SASPA) and Pak Lx Luminex technology with the monoclonal antibody immobilization of platelet antigens assay (MAIPA) to detect platelet alloantibodies
- Measurement of the inflammatory response in the early postoperative period after hip and knee arthroplasty
- Whole blood thromboelastometry profiles in women with preeclampsia
- Increased plasma soluble urokinase plasminogen activator receptor levels in systemic sclerosis: possible association with microvascular abnormalities and extent of fibrosis
- Reference Values and Biological Variations
- Reference ranges of serum bile acids in children and adolescents
- Infectious Diseases
- Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates with infection
- Cardiovascular Diseases
- Head-to-head comparison of 10 natriuretic peptide assays
- Prognostic role of BNP in children undergoing surgery for congenital heart disease: analysis of prediction models incorporating standard risk factors
- Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death
- Identification of molecular species of oxidized triglyceride in plasma and its distribution in lipoproteins
- A new formula for estimation of low-density lipoprotein cholesterol in an ethnic Chinese population
- Letter to the Editors
- Laboratory medicine: let’s say it is the mirror of science (and medicine)
- The economic burden of hemolysis
- Acute effects of conventional and extended hemodialysis and hemodiafiltration on high-sensitivity cardiac troponins
- Cuvette carryover with the gentamicin assay on the Beckman AU480 analyser
- Comparison study of two commercially available methods for the determination of golimumab and anti-golimumab antibody levels in patients with rheumatic diseases
- Automated alkaline-pH electrophoresis followed by densitometry does not correlate with cation-exchange (CE)-HPLC in quantification of HbA2 and variant hemoglobins
- Progression from light chain myeloma to secondary plasma cell leukemia accompanied by peripheral blood eosinophilia
- Harmonization of results has not been fully achieved for serum immunoglobulin measurements
- The risk of macrovascular complications in subjects genotyped for common IL-6 gene and TNF-α gene variants
- Comparison of nucleated red blood cell count with four commercial hematological analyzers
- Reply to: The risk of macrovascular complications in subjects genotyped for common IL-6 gene and TNF-α gene variants
- Congress Abstracts
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- 47th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
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