TUMOR-NECROSIS-FACTOR-ALPHA LEVELS IN PLASMA AND WHOLE-BLOOD CULTURE IN DENGUE-INFECTED PATIENTS - RELATIONSHIP BETWEEN VIRUS DETECTION ANDPREEXISTING SPECIFIC ANTIBODIES

The pathogenesis of dengue hemorrhagic fever (DHF) is not well known, but the role of host factors has been suggested. The level of immunore active circulating and cell-generated tumor necrosis factor alpha (TNF alpha) was studied in 35 patients with DHF; its relationship with vir us isolation and/or genome detection by reverse transcription polymera se chain reaction (RT-PCR) and specific antibodies were detected by he magglutination inhibition (HI). Large variation of TNF alpha plasma le vels 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 prod uction of TNF alpha by heparinized whole-blood culture compared with c ontrols also had elevated levels of TNF alpha in the plasma. The TNF a lpha values in lipopolysaccharide and phytohemagglutinin heparinized w hole-blood cultures were not higher in patients than in controls, but low TNF alpha levels were obtained in three out of 30 patients. An inv erse correlation was observed between spontaneous in vitro TNF alpha p roduction and viral replication, which raises the issue of the antivir al effect of TNF alpha in dengue infection. The results do not support the hypothesis of the role of antibody-dependent enhancement giving r ise to increased viremic titers and production of TNF alpha in patient s. The present study demonstrates the activation of the TNF alpha-prod ucing cells in dengue-infected patients and suggests further investiga tion to define the mechanism and the role of TNF alpha in the pathogen esis of dengue virus infection. (C) 1998 Wiley-Liss, Inc.