title: A BALB/c mouse model shows that liver involvement in dengue disease is immune-mediated.
abstract: In the present study, BALB/c mice were used to develop a model for the hepatic injury associated to dengue infection. Histological analysis after subcutaneous inoculation with a low viral dose of dengue-2 virus showed Kupffer cell hyperplasia and an increased inflammatory cellular infiltrate next to the bile ducts on days 5, 7 and 14 post-inoculation, mainly characterized by the presence of mononuclear cells. The liver mRNA transcription level of IL-1β was highest on the 5th day post-infection (p.i.) and decreased by the 21st day, TNF-α showed a peak of mRNA transcription after 14 days p.i. coinciding with the regression of cellular infiltrates and elevated expression of TGF-β mRNA. Serum AST and ALT levels were slightly elevated at 7 and 14 days post-infection. Dengue-2 RNA levels were undetectable in the liver on any of the days following inoculation. Our observations suggest that, as it is true for humans, the animals undergo a transient and slight liver inflammation, probably due to local cytokine production and cellular infiltration in the liver.
authors.affiliation: Program of Graduate Studies on Applied and Basic Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Rafael Freitas de Oliveira
authors.initials: RF
authors.lastname: França
authors.forename: Sérgio
authors.initials: S
authors.lastname: Zucoloto
authors.forename: Benedito Antônio Lopes
authors.initials: BA
authors.lastname: da Fonseca
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003715:Dengue / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology* / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D014158:Transcription, Genetic
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D012367:RNA, Viral