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Journal of Tropical Medicine
Volume 2014, Article ID 901276, 9 pages
Research Article

Elevated Dengue Virus Nonstructural Protein 1 Serum Levels and Altered Toll-Like Receptor 4 Expression, Nitric Oxide, and Tumor Necrosis Factor Alpha Production in Dengue Hemorrhagic Fever Patients

1Institute of Health Sciences, Laboratory of Cellular Activation, Federal University of Triângulo Mineiro, 38025-350 Uberaba, MG, Brazil
2Institute of Health Sciences, Department of Infectious and Parasitic Diseases, Federal University of Triângulo Mineiro, 38025-350 Uberaba, MG, Brazil
3Human Immunology Research Group, Technical Health School, Federal University of Paraiba (UFPB), 58051-900 João Pessoa, PB, Brazil

Received 18 August 2014; Revised 18 November 2014; Accepted 25 November 2014; Published 11 December 2014

Academic Editor: Jean-Paul Gonzalez

Copyright © 2014 Denise Maciel Carvalho et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. During dengue virus (DV) infection, monocytes produce tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) which might be critical to immunopathogenesis. Since intensity of DV replication may determine clinical outcomes, it is important to know the effects of viral nonstructural protein 1 (NS1) on innate immune parameters of infected patients. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1) serum levels and innate immune response (TLR4 expression and TNF-α/NO production) of DV infected patients presenting different clinical outcomes. Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA), TNF-α production by peripheral blood mononuclear cells (PBMCs), and TLR4 expression on CD14+ cells from 37 dengue patients and 20 healthy controls. Early in infection, increased expression of TLR4 in monocytes of patients with dengue fever (DF) was detected compared to patients with dengue hemorrhagic fever (DHF). Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum levels during the acute febrile phase and a reduced response to TLR4 stimulation by LPS (with a reduced TNF-α production) when compared to DF patients. Conclusions/Significance. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes.