title: Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity.
abstract: BACKGROUND
  Obesity is associated with a high circulating leptin level and severe 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) infection. The mechanism for severe lung injury in obese patients and the specific treatment strategy remain elusive.
  
  
  METHODS
  We studied the pathogenesis of A(H1N1)pdm09 infection in a mouse model of diet-induced obesity.
  
  
  RESULTS
  Obese mice had significantly higher initial pulmonary viral titer and mortality after challenge with A(H1N1)pdm09, compared with age-matched lean mice. Compared with lean mice, obese mice had heightened proinflammatory cytokine and chemokine levels and more severe pulmonary inflammatory damage. Furthermore, obese mice had a higher preexisting serum leptin level but a lower preexisting adiponectin level. Recombinant mouse leptin increased the interleukin 6 (IL-6) messenger RNA expression in mouse single-lung-cell preparations, mouse macrophages, and mouse lung epithelial cell lines infected with A(H1N1)pdm09. Administration of anti-leptin antibody improved the survival of infected obese mice, with associated reductions in pulmonary levels of the proinflammatory cytokines IL-6 and interleukin 1β but not the pulmonary viral titer.
  
  
  CONCLUSIONS
  Our findings suggest that preexisting high levels of circulating leptin contribute to the development of severe lung injury by A(H1N1)pdm09 in mice with diet-induced obesity. The therapeutic strategy of leptin neutralization for the reduction of proinflammatory responses and pulmonary damage in obese patients warrants further investigations.
authors: Carol Yu Centre for Infection and Division of Infectious Diseases, Department of Microbiology, University of Hong Kong, Queen Mary Hospital, Pokfulam Rd, Pokfulam, Hong Kong SAR, China.
authors: Anna J X
authors: AJ
authors: Zhang
authors: Kelvin K W
authors: KK
authors: To
authors: Can
authors: C
authors: Li
authors: Candy C Y
authors: CC
authors: Lau
authors: Vincent K M
authors: VK
authors: Poon
authors: Chris C S
authors: CC
authors: Chan
authors: Bo-Jian
authors: BJ
authors: Zheng
authors: Ivan F N
authors: IF
authors: Hung
authors: Karen S L
authors: KS
authors: Lam
authors: Aimin
authors: A
authors: Xu
authors: Kwok-Yung
authors: KY
authors: Yuen
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004848:Epithelium / Q000276:immunology / Q000473:pathology; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D020738:Leptin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000276:immunology* / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology; D058873:Pandemics; D011014:Pneumonia / Q000276:immunology / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D019562:Viral Load
chemical_list: D000906:Antibodies; D053583:Interleukin-1beta; D015850:Interleukin-6; D020738:Leptin; D012333:RNA, Messenger; D011994:Recombinant Proteins; C577686:interleukin-6, mouse