TITLE

Leptin Mediates the Pathogenesis of Severe 2009 Pandemic Influenza A(H1N1) Infection Associated With Cytokine Dysregulation in Mice With Diet-Induced Obesity

AUTHOR(S)
Zhang, Anna J. X.; To, Kelvin K. W.; Li, Can; Lau, Candy C. Y.; Poon, Vincent K. M.; Chan, Chris C. S.; Zheng, Bo-Jian; Hung, Ivan F. N.; Lam, Karen S. L.; Xu, Aimin; Yuen, Kwok-Yung
PUB. DATE
April 2013
SOURCE
Journal of Infectious Diseases;Apr2013, Vol. 207 Issue 8, p1270
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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.
ACCESSION #
86428995

 

Related Articles

  • Characterization of cross protection of Swine-Origin Influenza Virus (S-OIV) H1N1 and reassortant H5N1 influenza vaccine in BALB/c mice given a single-dose vaccination. Lin, Hui-Tsu; Chuang, Chuan-Chang; Wu, Hsieh-Ling; Chu, Der-Ming; Wang, Yeau-Ching // Journal of Biomedical Science;2013, Vol. 20 Issue 1, p1 

    Background: Influenza virus has antigen drift and antigen shift effect, vaccination with some influenza vaccine might not induce sufficient immunity for host to the threat of other influenza virus strains. S-OIV H1N1 and H5N1 influenza vaccines in single-dose immunization were evaluated in mice...

  • Influenza A Strain-Dependent Pathogenesis in Fatal H1N1 and H5N1 Subtype Infections of Mice. Garigliany, Mutien-Marie; Habyarimana, Adélite; Lambrecht, Bénédicte; Van De Paar, Els; Cornet, Anne; Van den Berg, Thierry; Desmecht, Daniel // Emerging Infectious Diseases;Apr2010, Vol. 16 Issue 4, p595 

    To determine if fatal infections caused by different highly virulent influenza A viruses share the same pathogenesis, we compared 2 different influenza A virus subtypes, H1N1 and H5N1. The subtypes, which had shown no pathogenicity in laboratory mice, were forced to evolve by serial passaging....

  • Influenza Antiviral Therapeutics. Mayburd, Anatoly L. // Recent Patents on Anti-Infective Drug Discovery;Jan2010, Vol. 5 Issue 1, p64 

    In this review, we conducted a landscaping study of the therapeutic anti-influenza agents, limiting the scope by exclusion of vaccines. The resulting 2800 patent publications were classified into 23 distinct technological sectors. The mechanism of action, the promise and drawbacks of the...

  • Influenza2010: Zoonotic Influenza and Human Health: Part-B.  // Journal of Molecular & Genetic Medicine (Library Publishing Medi;2010, Vol. 4 Issue 1, p262 

    The article presents abstracts on medical topics which include the emergence of pandemic (H1N1) 2009 virus (pH1N1) in humans and the evaluation of two commercial lateral flow devices (LFDs) to detect H5N1 highly pathogenic avian influenza (HPAI) infections in the poultry of Egypt.

  • 2009 pandemic H1N1 influenza A virus strains display differential pathogenicity in C57BL/6J but not BALB/c mice. Otte, Anna; Gabriel, Gülsah // Virulence;Nov2011, Vol. 2 Issue 6, p1 

    Influenza A viruses are the causative agents of annual epidemics and occasional pandemics. The pathogenicity of influenza viruses is determined by complex interplay of viral and host factors. While some knowledge exists on viral determinants of pathogenicity, little is known on the host factors...

  • Pre- and Postexposure Use of Human Monoclonal Antibody against H5N1 and H1N1 Influenza Virus in Mice: Viable Alternative to Oseltamivir. Koudstaal, Wouter; Koldijk, Martin H.; Brakenhoff, Just P. J.; Cornelissen, Lisette A. H. M.; Weverling, Gerrit Jan; Friesen, Robert H. E.; Goudsmit, Jaap // Journal of Infectious Diseases;12/15/2009, Vol. 200 Issue 12, p1870 

    New strategies to prevent and treat influenza virus infections are urgently needed. A recently discovered class of monoclonal antibodies (mAbs) neutralizing an unprecedented spectrum of influenza virus subtypes may have the potential for future use in humans. Here, we assess the efficacies of...

  • Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenz A Infection. Huang, Yongsheng; Zaas, Aimee K.; Rao, Arvind; Dobigeon, Nicolas; Woolf, Peter J.; Veldman, Timothy; Øien, N. Christine; McClain, Micah T.; Varkey, Jay B.; Nicholson, Bradley; Carin, Lawrence; Kingsmore, Stephen; Woods, Christopher W.; Ginsburg, Geoffrey S.; Hero III, Alfred O. // PLoS Genetics;Aug2011, Vol. 7 Issue 8, Special section p1 

    Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A...

  • Vaccines against Seasonal and Pandemic Influenza and the Implications of Changes in Substrates for Virus Production. Minor, Philip D. // Clinical Infectious Diseases;2/15/2010, Vol. 50 Issue 4, p560 

    Influenza virus changes constantly, making vaccine production challenging. Changing the growth substrate from eggs to cell culture raises issues at all stages of the process, from surveillance to the assay of vaccines. The pandemic threat-first H5N1, then H1N1-encouraged a review of methods and...

  • Comparison of Patients Hospitalized With Influenza A Subtypes H7N9, H5N1, and 2009 Pandemic H1N1. Wang, Chen; Yu, Hongjie; Horby, Peter W.; Cao, Bin; Wu, Peng; Yang, Shigui; Gao, Hainv; Li, Hui; Tsang, Tim K.; Liao, Qiaohong; Gao, Zhancheng; Ip, Dennis K. M.; Jia, Hongyu; Jiang, Hui; Liu, Bo; Ni, Michael Y.; Dai, Xiahong; Liu, Fengfeng; Van Kinh, Nguyen; Liem, Nguyen Thanh // Clinical Infectious Diseases;Apr2014, Vol. 58 Issue 8, p1095 

    Hospitalization with H7N9 virus infection is associated with older age and chronic heart disease, and patients have a longer duration of hospitalization than patients with H5N1 or pH1N1. This suggests that host factors are an important contributor to H7N9 severity.Background. Influenza A(H7N9)...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics