• 1.

    International Vaccine Institute, 2008. The Pediatric Dengue Vaccine Initiative. Vaccines, Children and a Better World Annual Report. Seoul: International Vaccine Institute, 2835.

    • Search Google Scholar
    • Export Citation
  • 2.

    World Health Organization, 2009. Dengue Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva: World Health Organization, 354.

    • Search Google Scholar
    • Export Citation
  • 3.

    Nielsen DG, 2009. The relationship of interacting immunological components in dengue pathogenesis. J Virol 6: 211.

  • 4.

    Singhasivanon P, Jacobson J, 2009. Dengue is a major global health problem. J Clin Virol 46: S1S2.

  • 5.

    Halstead SB, 2007. Dengue. Lancet 370: 16441652.

  • 6.

    Martina BE, Koraka P, Osterhaus AD, 2009. Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 22: 564581.

  • 7.

    Srikiatkhachorn A, Ajariyakhajorn C, Endy TP, Kalayanarooj S, Libraty DH, Green S, Ennis FA, Rothman AL, 2007. Virus-induced decline in soluble vascular endothelial growth receptor 2 is associated with plasma leakage in dengue hemorrhagic fever. J Virol 1: 15921600.

    • Search Google Scholar
    • Export Citation
  • 8.

    Basu A, Chaturvedi UC, 2008. Vascular endothelium: the battlefield of dengue viruses. FEMS Immunol Med Microbiol 53: 287299.

  • 9.

    Srikiatkhachorn A, Ajariyakhajorn C, Endy TP, Kalayanarooj S, Libraty DH, Green S, Ennis FA, Rothman AL, 2007. Virus-induced decline in soluble vascular endothelial growth receptor 2 is associated with plasma leakage in dengue hemorrhagic fever. J Virol 1: 15921600.

    • Search Google Scholar
    • Export Citation
  • 10.

    Chaturvedi UC, Agarwal R, Elbishbishi EA, Mustafa AS, 2000. Cytokine cascade in dengue hemorrhagic fever: implications for pathogenesis. FEMS Immunol Med Microbiol 28: 183188.

    • Search Google Scholar
    • Export Citation
  • 11.

    Wang SM, Sekaran SD, 2010. Early diagnosis of dengue infection using a commercial dengue duo rapid test kit for the detection of NS1, IgM, IgG. Am J Trop Med Hyg 83: 690695.

    • Search Google Scholar
    • Export Citation
  • 12.

    World Medical Association Declaration of Helsinki, 2000. Ethical principles for medical research involving human subjects. JAMA 24: 30433045.

    • Search Google Scholar
    • Export Citation
  • 13.

    Rothman AL, Ennis FA, 1999. Immunopathogenesis of dengue hemorrhagic fever. Virology 257: 16.

  • 14.

    Mongkolsapaya J, Duangchinda T, Dejnirattisai W, Vasanawathana S, Avirutnan P, Jairungsri A, Khemnu N, Tangthawornchaikul N, Chotiyarnwong P, Sae-Jang K, Koch M, Jones Y, McMichael A, Xu X, Malasit P, Screaton G, 2006. T cell responses in dengue hemorrhagic fever: are cross-reactive T cells suboptimal? J Immunol 176: 38213829.

    • Search Google Scholar
    • Export Citation
  • 15.

    Chaturvedi UC, Agarwal R, Elbishbishi EA, Mustafa AS, 2000. Cytokine cascade in dengue hemorrhagic fever: implications for pathogenesis. FEMS Immunol Med Microbiol 28: 183188.

    • Search Google Scholar
    • Export Citation
  • 16.

    Mustafa AS, Elbishbishi EA, Agarwal R, Chaturvedi UC, 2001. Elevated levels of interleukin-13 and IL-18 in patients with dengue hemorrhagic fever. FEMS Immunol Med Microbiol 30: 229233.

    • Search Google Scholar
    • Export Citation
  • 17.

    Priyadarshini D, Gadia RR, Tripathy A, Gurukumar KR, Bhagat A, Patwardhan S, Mokashi N, Vaidva D, Shah PS, Cecelia D, 2010. Clinical findings and pro-inflammatory cytokines in dengue patients in western India: a facility-based study. PLoS ONE 5: e8709.

    • Search Google Scholar
    • Export Citation
  • 18.

    Shresta S, 2012. Role of complement in dengue virus infection: protection or pathogenesis. mBio 3: e0000312.

  • 19.

    Kanlaya R, Pattanakitsakul S, Sinchaikul S, Chen ST, Thongboonkerd V, 2009. Alterations in actin cytoskeletal assembly and junctional protein complexes in human endothelial cells induced by dengue virus infection and mimicry of leukocyte transendothelial migration. J Proteome Res 8: 25512562.

    • Search Google Scholar
    • Export Citation
  • 20.

    Crone C, 1986. Modulation of solute permeability in microvascular endothelium. Fed Proc 45: 7783.

  • 21.

    Tseng CS, Lo HW, Teng HC, Lo WC, Ker CG, 2005. Elevated levels of plasma VEGF in patients with dengue hemorrhagic fever. FEMS Immunol Med Microbiol 43: 99102.

    • Search Google Scholar
    • Export Citation
  • 22.

    Huang YH, Lei HY, Liu HS, Lin YS, Liu CC, Yeh TM, 2000. Dengue virus infects human endothelial cells and induces IL-6 and IL-8 production. Am J Trop Med Hyg 63: 7175.

    • Search Google Scholar
    • Export Citation
  • 23.

    Avirutnan P, Malasit P, Seliger B, Bhakdi S, Husmann M, 1998. Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis. J Immunol 161: 63386346.

    • Search Google Scholar
    • Export Citation
 
 
 
 

 

 
 

 

 

 

 

 

 

Cytokine Factors Present in Dengue Patient Sera Induces Alterations of Junctional Proteins in Human Endothelial Cells

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  • Department of Medical Microbiology, Department of Medicine, and Department of Pediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia

Plasma leakage in severe dengue has been postulated to be associated with skewed cytokine immune responses. In this study, the association of cytokines with vascular permeability in dengue patients was investigated. Human serum samples collected from 48 persons (13 with dengue fever, 29 with dengue hemorrhagic fever, and 6 healthy) were subjected to cytokines analysis by using Luminex Multiplex Technology. Selected serum samples from patients with dengue hemorrhagic fever sera and recombinant human cytokines were then tested for roles on inducing vascular permeability by treatment of human umbilical vein endothelial cells. Confocal immunofluorescence staining indicated morphologic alteration of human umbilical vein endothelial cells treated with serum samples from patients with dengue hemorrhagic fever compared with serum samples from healthy persons. The findings suggest that cytokines produced during dengue hemorrhagic infections could induce alterations in the vascular endothelium, which may play a fundamental role in the pathophysiology of dengue.

Author Notes

* Address correspondence to Shamala Devi Sekaran, Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. E-mail: shamalamy@yahoo.com

Financial support: This study was supported by University of Malaya research grants UMRG RG081-09HTM and HIRG J-00000-73560.

Disclosure: None of the authors have any conflicts of interest.

Authors' addresses: Ramapraba Appanna and Shamala Devi Sekaran, Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia, E-mails: ag_praba@yahoo.com and shamalaya@yahoo.com. Seok Mui Wang, Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia, E-mail: seokmuiwang@yahoo.com. Sasheela A. Ponnampalavanar, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia, E-mail: sasheela@um.edu.my. Lucy Chai See Lum, Department of Pediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia, E-mail: lumcs@um.edu.my.

Reprint requests: Shamala Devi Sekaran, Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia, E-mail: shamalaya@yahoo.com.

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