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J Infect Dis. 2013 Apr 15;207(8):1270-80. doi: 10.1093/infdis/jit031. Epub 2013 Jan 16.

Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity.

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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.



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.


We studied the pathogenesis of A(H1N1)pdm09 infection in a mouse model of diet-induced obesity.


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.


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.

[Indexed for MEDLINE]

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