title: Leptin downregulates LPS-induced lung injury: role of corticosterone and insulin.
abstract: OBJECTIVE
  We investigated the effects of leptin in the development of lipopolysaccharide (LPS)-induced acute lung inflammation (ALI) in lean mice.
  
  
  METHODS
  Mice were administered leptin (1.0µg/g) or leptin (1.0µg/g) followed by LPS (1.5µg/g) intranasally. Additionally, some animals were given LPS (1.5µg/g) or saline intranasally alone, as a control. Tissue samples and fluids were collected six hours after instillation.
  
  
  RESULTS
  We demonstrated that leptin alone did not induce any injury. Local LPS exposure resulted in significant acute lung inflammation, characterized by a substantial increase in total cells, mainly neutrophils, in bronchoalveolar lavages (BAL). We also observed a significant lymphocyte influx into the lungs associated with enhanced lung expression of chemokines and cytokines (KC, RANTES, TNF-α, IFN-γ, GM-CSF and VEGF). LPS-induced ALI was characterized by the enhanced expression of ICAM-1 and iNOS in the lungs. Mice that received LPS showed an increase in insulin levels. Leptin, when administered prior to LPS instillation, abolished all of these effects. LPS induced an increase in corticosterone levels, and leptin potentiated this event.
  
  
  CONCLUSIONS
  These data suggest that exogenous leptin may promote protection during sepsis, and downregulation of the insulin levels and upregulation of corticosterone may be important mechanisms in the amelioration of LPS-induced ALI.
authors.affiliation: Laboratory of Hypertension, Dept of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Maristella A
authors.initials: MA
authors.lastname: Landgraf
authors.forename: Reinaldo C
authors.initials: RC
authors.lastname: Silva
authors.forename: Matheus
authors.initials: M
authors.lastname: Corrêa-Costa
authors.forename: Meire I
authors.initials: MI
authors.lastname: Hiyane
authors.forename: Maria Helena C
authors.initials: MH
authors.lastname: Carvalho
authors.forename: Richardt G
authors.initials: RG
authors.lastname: Landgraf
authors.forename: Niels O S
authors.initials: NO
authors.lastname: Câmara
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D007328:Insulin / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D020738:Leptin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis
chemical_list: D016207:Cytokines; C090509:Icam1 protein, mouse; D007328:Insulin; D020738:Leptin; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D003345:Corticosterone