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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.

Author information

1
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.

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.

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 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.

PMID:
23325916
DOI:
10.1093/infdis/jit031
[Indexed for MEDLINE]

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