Cytokine factors present in dengue patient sera induces alterations of junctional proteins in human endothelial cells.

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.

[1]  A. Basu,et al.  Vascular endothelium: the battlefield of dengue viruses , 2008, FEMS immunology and medical microbiology.

[2]  Albert D. M. E. Osterhaus,et al.  Dengue Virus Pathogenesis: an Integrated View , 2009, Clinical Microbiology Reviews.

[3]  S. Sekaran,et al.  Early diagnosis of Dengue infection using a commercial Dengue Duo rapid test kit for the detection of NS1, IGM, and IGG. , 2010, The American journal of tropical medicine and hygiene.

[4]  S. Shresta.  Role of Complement in Dengue Virus Infection: Protection or Pathogenesis? , 2012, mBio.

[5]  A. Mustafa,et al.  Elevated levels of interleukin-13 and IL-18 in patients with dengue hemorrhagic fever. , 2001, FEMS immunology and medical microbiology.

[6]  P. Singhasivanon,et al.  Dengue is a major global health problem. Foreword. , 2009, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[7]  S. Kalayanarooj,et al.  Virus-Induced Decline in Soluble Vascular Endothelial Growth Receptor 2 Is Associated with Plasma Leakage in Dengue Hemorrhagic Fever , 2006, Journal of Virology.

[8]  C. Crone.  Modulation of solute permeability in microvascular endothelium. , 1986, Federation proceedings.

[9]  S. Eckstein.  Ethical principles for medical research involving human subjects. , 2001, European journal of emergency medicine : official journal of the European Society for Emergency Medicine.

[10]  B. Seliger,et al.  Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis. , 1998, Journal of immunology.

[11]  A. Rothman,et al.  Immunopathogenesis of Dengue hemorrhagic fever. , 1999, Virology.

[12]  Shui-Tein Chen,et al.  Alterations in actin cytoskeletal assembly and junctional protein complexes in human endothelial cells induced by dengue virus infection and mimicry of leukocyte transendothelial migration. , 2009, Journal of proteome research.

[13]  C. Ker,et al.  Elevated levels of plasma VEGF in patients with dengue hemorrhagic fever. , 2005, FEMS immunology and medical microbiology.

[14]  David G Nielsen.  The relationship of interacting immunological components in dengue pathogenesis , 2009, Virology Journal.

[15]  A. Tripathy,et al.  Clinical Findings and Pro-Inflammatory Cytokines in Dengue Patients in Western India: A Facility-Based Study , 2010, PloS one.

[16]  Y. S. Lin,et al.  Dengue virus infects human endothelial cells and induces IL-6 and IL-8 production. , 2000, The American journal of tropical medicine and hygiene.

[17]  A. Mustafa,et al.  Cytokine cascade in dengue hemorrhagic fever: implications for pathogenesis. , 2000, FEMS immunology and medical microbiology.