title: Immunopathogenesis of dengue hemorrhagic fever: contribution to the study of human liver lesions.
abstract: Dengue infection is an important tropical disease worldwide. The host immune response has been studied in order to better understand lesion mechanisms. It was performed an immunohistochemical study in 14 specimens of liver from patients with dengue hemorrhagic fever (DHF) to characterize cytokines and some factors present in liver lesions and their possible role in the pathogenesis of hepatic injury. Portal tract and hepatic acinus presented high expression of TLR2, TLR3, IL6, and granzyme B. Hepatic acinus also presented iNOS, IL18, and TGF-beta. Cells expressing IL12, IL13, JAk1, STAT1, and NF-κB were rarely visualized. Treg cells foxp3+ were absent. TLR2 and TLR3 seem to participate in cellular activation and cytokine production. Cytotoxic response seems to play a role. Although TGF-beta promotes the activation of Foxp3+ regulatory T cells, IL6 can significantly suppresses their generation. The expression of Treg cells is diminished probably as a result of the high frequency of these cytokines. Both cytokines play a role in the increased vascular permeability and edema observed in dengue liver specimens, with consequent plasma leakage and severity of the disease. It was observed a regular expression of IL-18 in hepatocytes and lymphocytes of the inflammatory infiltrate in portal tract, which reflects the acute inflammatory response that occurs in the liver and contributes to hepatic injury. At least in part, the increased number of cells expressing IL-18 could play a role of "up" regulation of FasL and correlate to the phenomenon of apoptosis, a mechanism of destruction of hepatocytes in DHF.
authors.affiliation: Faculdade de Medicina da Universidade de São Paulo, Laboratório da Disciplina de Patologia de Moléstias Transmissíveis, Departamento de Patologia, São Paulo, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Pagliari
authors.forename: Juarez Antonio Simões
authors.initials: JA
authors.lastname: Quaresma
authors.forename: Elaine Raniero
authors.initials: ER
authors.lastname: Fernandes
authors.forename: Felipe Weisshaupt
authors.initials: FW
authors.lastname: Stegun
authors.forename: Roosecelis Araújo
authors.initials: RA
authors.lastname: Brasil
authors.forename: Heitor Franco
authors.initials: HF
authors.lastname: de Andrade
authors.forename: Vera
authors.initials: V
authors.lastname: Barros
authors.forename: Pedro Fernando C
authors.initials: PF
authors.lastname: Vasconcelos
authors.forename: Maria Irma Seixas
authors.initials: MI
authors.lastname: Duarte
mesh_terms: D017209:Apoptosis; D016207:Cytokines / Q000032:analysis; D022781:Hepatocytes / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000032:analysis; D008099:Liver / Q000473:pathology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D008853:Microscopy; D019595:Severe Dengue / Q000276:immunology* / Q000473:pathology*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors
keywords: cytokines; dengue hemorrhagic fever; immunopathology; liver