title: Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats.
abstract: BACKGROUND
  Our study has shown that plasma levels of ghrelin, a stomach-derived peptide, are significantly reduced in sepsis, and that ghrelin administration improves organ blood flow via a nuclear factor (NF)-kappaB-dependent pathway. However, it remains unknown whether ghrelin has any protective effects on severe sepsis-induced acute lung injury (ALI) and, if so, whether inhibition of NF-kappaB plays any role in it.
  
  
  OBJECTIVE
  To test the hypothesis that ghrelin reduces severe sepsis-induced ALI and mortality through inhibition of NF-kappaB.
  
  
  METHODS
  Sepsis was induced in rats by cecal ligation and puncture (CLP). Five hours after CLP, a bolus intravenous injection of 2 nmol of ghrelin was followed by continuous infusion of 12 nmol of ghrelin via a minipump for 15 hours. Samples were harvested 20 hours post-CLP (i.e., severe sepsis). Pulmonary levels of ghrelin and proinflammatory cytokines were measured by ELISA. NF-kappaB p65 and IkappaBalpha expression and NF-kappaB activity were measured by Western blot analysis and ELISA, respectively. Pulmonary blood flow was measured with radioactive microspheres. In additional animals, the necrotic cecum was excised 20 hours post-CLP and 10-day survival was recorded.
  
  
  RESULTS
  Pulmonary levels of ghrelin decreased significantly 20 hours post-CLP. Ghrelin administration restored pulmonary levels of ghrelin, reduced lung injury, increased pulmonary blood flow, down-regulated proinflammatory cytokines, inhibited NF-kappaB activation, and improved survival in sepsis. Administration of a specific ghrelin receptor antagonist worsened the survival rate after CLP and cecal excision.
  
  
  CONCLUSIONS
  Ghrelin can be developed as a novel treatment for severe sepsis-induced ALI. The protective effect of ghrelin is mediated through inhibition of NF-kappaB.
authors.affiliation: Department of Surgery, North Shore University Hospital, Manhasset, New York, USA.
authors.forename: Rongqian
authors.initials: R
authors.lastname: Wu
authors.forename: Weifeng
authors.initials: W
authors.lastname: Dong
authors.forename: Mian
authors.initials: M
authors.lastname: Zhou
authors.forename: Fangming
authors.initials: F
authors.lastname: Zhang
authors.forename: Corrado P
authors.initials: CP
authors.lastname: Marini
authors.forename: Thanjavur S
authors.initials: TS
authors.lastname: Ravikumar
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D054439:Ghrelin / Q000378:metabolism / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D018805:Sepsis / Q000150:complications*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D054439:Ghrelin; D015850:Interleukin-6; D016328:NF-kappa B; D018377:Neurotransmitter Agents; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; C045800:substance P, Phe(5)-Trp(7,9)-Leu(11)-