title: The effect of ghrelin upon the early immune response in lean and obese mice during sepsis.
abstract: BACKGROUND
  It is well established that obesity-related hormones can have modulatory effects associated with the immune response. Ghrelin, a hormone mainly derived from endocrine cells of the gastric mucosa, regulates appetite, energy expenditure and body weight counteracting leptin, a hormone mainly derived from adipocytes. Additionally, receptors of both have been detected on immune cells and demonstrated an immune regulatory function during sepsis.
  
  
  METHODS
  In the present study, the effect of peripheral ghrelin administration on early immune response and survival was investigated with lean mice and mice with diet-induced obesity using cecal ligation and puncture to induce sepsis.
  
  
  RESULTS
  In the obese group, we found that ghrelin treatment improved survival, ameliorated hypothermia, and increased hyperleptinemia as compared to the lean controls. We also observed that ghrelin treatment divergently regulated serum IL-1ß and TNF-α concentrations in both lean and obese septic mice. Ghrelin treatment initially decreased but later resulted in increased bacteriaemia in lean mice while having no impact upon obese mice. Similarly, ghrelin treatment increased early neutrophil oxidative burst while causing a decrease 48 hours after sepsis inducement.
  
  
  CONCLUSIONS
  In conclusion, as the immune response to sepsis temporally changes, ghrelin treatment differentially mediates this response. Specifically, we observed that ghrelin conferred protective effects during the early phase of sepsis, but during the later phase deteriorated immune response and outcome. These adverse effects were more pronounced upon lean mice as compared to obese mice.
authors.affiliation: Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Siegl
authors.affiliation: Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Emily F
authors.initials: EF
authors.lastname: Midura
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Annecke
authors.affiliation: Department of Anaesthesiology, University Hospital Munich (LMU), Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Conzen
authors.affiliation: Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
authors.affiliation: Department of Anaesthesiology, University Hospital Munich (LMU), Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Tschoep
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D054439:Ghrelin / Q000008:administration & dosage* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000097:blood*; D020738:Leptin / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009504:Neutrophils / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000276:immunology*; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D054439:Ghrelin; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha
references.citation: Nature. 1999 Dec 9;402(6762):656-60
references.pmid: 10604470
references.citation: Am J Physiol. 1997 May;272(5 Pt 2):H2219-26
references.pmid: 9176289
references.citation: Science. 1995 Jul 28;269(5223):540-3
references.pmid: 7624776
references.citation: Regul Pept. 2004 Nov 15;122(3):173-8
references.pmid: 15491788
references.citation: J Clin Endocrinol Metab. 1998 Jan;83(1):280-3
references.pmid: 9435456
references.citation: Am J Physiol. 1999 Jan;276(1 Pt 2):R136-42
references.pmid: 9887187
references.citation: J Am Diet Assoc. 1999 Mar;99(3):294-9
references.pmid: 10076580
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):7047-52
references.pmid: 10359836
references.citation: J Clin Invest. 1999 Oct;104(8):1051-9
references.pmid: 10525043
references.citation: Crit Care Med. 2005 Dec;33(12 Suppl):S468-71
references.pmid: 16340424
references.citation: Eur Surg Res. 2005 Nov-Dec;37(6):354-9
references.pmid: 16465060
references.citation: Microbes Infect. 2006 Apr;8(5):1382-9
references.pmid: 16679040
references.citation: Lancet Infect Dis. 2006 Jul;6(7):438-46
references.pmid: 16790384
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Oct;291(4):G611-20
references.pmid: 16959954
references.citation: Ann Surg. 2007 Mar;245(3):480-6
references.pmid: 17435556
references.citation: J Nutr. 2007 May;137(5):1236-43
references.pmid: 17449587
references.citation: Am J Respir Crit Care Med. 2007 Oct 15;176(8):805-13
references.pmid: 17626913
references.citation: Surgery. 2008 Mar;143(3):334-42
references.pmid: 18291254
references.citation: J Leukoc Biol. 2008 Mar;83(3):581-8
references.pmid: 18063696
references.citation: Crit Care Med. 2008 Mar;36(3):828-33
references.pmid: 18431270
references.citation: Shock. 2008 May;29(5):591-7
references.pmid: 17885647
references.citation: Pol Arch Med Wewn. 2008 Mar;118(3):92-5
references.pmid: 18476452
references.citation: J Immunol. 2008 Jun 15;180(12):8369-77
references.pmid: 18523304
references.citation: J Clin Endocrinol Metab. 2008 Nov;93(11 Suppl 1):S9-30
references.pmid: 18987276
references.citation: Am J Physiol Renal Physiol. 2009 Oct;297(4):F1032-7
references.pmid: 19625378
references.citation: Methods Mol Biol. 2010;602:411-5
references.pmid: 20012411
references.citation: J Neurosci. 2010 Apr 28;30(17):6036-47
references.pmid: 20427662
references.citation: Endocr Metab Immune Disord Drug Targets. 2010 Dec;10(4):336-47
references.pmid: 20923403
references.citation: Physiol Behav. 2011 Mar 28;102(5):481-4
references.pmid: 21163280
references.citation: Physiol Behav. 2011 Nov 30;105(1):43-51
references.pmid: 21513721
references.citation: Surgery. 2012 Jan;151(1):37-47
references.pmid: 21943641
references.citation: Int Immunopharmacol. 2012 Aug;13(4):440-5
references.pmid: 22575870
references.citation: Methods Enzymol. 2012;514:355-70
references.pmid: 22975064
references.citation: Anesthesiology. 2014 Jul;121(1):98-114
references.pmid: 24595112
references.citation: BMC Infect Dis. 2013;13:377
references.pmid: 23957291
references.citation: Shock. 1995 Apr;3(4):235-51
references.pmid: 7600191
references.citation: Endocrinology. 2002 Jan;143(1):155-62
references.pmid: 11751604
references.citation: Endocrinology. 2002 Jan;143(1):185-90
references.pmid: 11751608
references.citation: Shock. 2002 Jun;17(6):463-7
references.pmid: 12069181
references.citation: Nutr Rev. 2002 Oct;60(10 Pt 2):S1-14; discussion S68-84, 85-7
references.pmid: 12403078
references.citation: Acta Pharmacol Sin. 2003 Jan;24(1):45-9
references.pmid: 12511228
references.citation: N Engl J Med. 2003 Jan 9;348(2):138-50
references.pmid: 12519925
references.citation: Shock. 2004 May;21(5):415-25
references.pmid: 15087817
references.citation: J Clin Invest. 2004 Jul;114(1):57-66
references.pmid: 15232612
references.citation: Am J Physiol Heart Circ Physiol. 2004 Sep;287(3):H1296-302
references.pmid: 15155262
references.citation: Intensive Care Med. 2000 Jun;26(6):716-21
references.pmid: 10945388