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10.1093/infdis/jit031

http://scihub22266oqcxt.onion/10.1093/infdis/jit031
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23325916!ä!23325916

suck abstract from ncbi


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pmid23325916      J+Infect+Dis 2013 ; 207 (8): 1270-80
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  • Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity #MMPMID23325916
  • Zhang AJ; To KK; Li C; Lau CC; Poon VK; Chan CC; Zheng BJ; Hung IF; Lam KS; Xu A; Yuen KY
  • J Infect Dis 2013[Apr]; 207 (8): 1270-80 PMID23325916show ga
  • 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. METHOD: 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 1beta 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.
  • |Animals[MESH]
  • |Antibodies/administration & dosage/immunology[MESH]
  • |Diet, High-Fat/adverse effects[MESH]
  • |Disease Models, Animal[MESH]
  • |Epithelium/immunology/pathology[MESH]
  • |Female[MESH]
  • |Influenza A Virus, H1N1 Subtype/*pathogenicity[MESH]
  • |Interleukin-1beta/immunology[MESH]
  • |Interleukin-6/genetics/*immunology[MESH]
  • |Kaplan-Meier Estimate[MESH]
  • |Leptin/*immunology/metabolism/pharmacology[MESH]
  • |Lung/immunology/pathology/virology[MESH]
  • |Macrophages/drug effects/immunology/virology[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Mice, Obese[MESH]
  • |Obesity/*immunology/virology[MESH]
  • |Orthomyxoviridae Infections/immunology/*pathology/virology[MESH]
  • |Pandemics[MESH]
  • |Pneumonia/immunology/pathology/virology[MESH]
  • |RNA, Messenger/analysis/genetics[MESH]
  • |Recombinant Proteins/immunology/pharmacology[MESH]


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