Didier Hober1, Trong Lan
Nguyen2, Lu Shen1, Do Quang Ha3, Vu Thi Que
Huong3, Samira Benyoucef1,
Thanh Hung Nguyen2, Thi Mai Phuong Bui2, Huynh Kim Loan3,
Bich Lien Le2,
Ahmed Bouzidi4, Donat De Groote5, Marie Thérèse Drouet6,
Vincent Deubel6 and
(1) Laboratory of Virology,
(2) Dengue Hemorrhagic Fever Department, Pediatric
Hospital No.1,
(3) Laboratory of Arbovirus, Pasteur Institute,
(4) Department of Research and Development, Laboratory
of Fractionization and Biotechnology,
(5) Department of Research and Development, Medgenix
Diagnostics SA,
(6)Unit of Arbovirus and virus of
hemorrhagic Fever Pasteur Institute,
The pathogenesis of dengue hemorrhagic fever (DHF) is not well known, but the role of host factors has been suggested. The level of immunoreactive circulating and cell-generated tumor necrosis factor alpha (TNFa) was studied in 35 patients with DHF; its relationship with virus isolation and / or genome detection by reverse transcription polymerase chain reaction (RT-PCR) and specific antibodies were detected by hemagglutination inhibition (HI). Large variation of TNFa plasma levels was obtained in dengue-infected patients at the same stage of the disease and at the same day after infection. Most of the patients (14 out of 17 patients) who displayed augmented spontaneous in vitro production of TNFa by heparinized whole-blood culture compared with controls also had elevated levels of TNFa in the plasma. The TNFa values in lipo-polysaccharide and phytohemagglutinin heparinized whole-blood cultures were not higher in patients than in controls, but low TNFa levels were obtained in three out of 30 patients. An inverse correlation was observed between spontaneous in vitro TNFa production and viral replication, which raises the issue of the antiviral effect of TNFa in dengue infection. The results do not support the hypothesis of the role of antibody-dependent enhancement giving rise to increased viremic titers and production of TNFa in patients. The present study demonstrates the activation of the TNFa-producing cells in dengue-infected patients and suggests further investigation to define the mechanism and the role of TNFa in the pathogenesis of dengue virus infection.