A BALB/c mouse model shows that liver involvement in dengue disease is immune-mediated.
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.
França
Rafael Freitas de Oliveira
RF
Program of Graduate Studies on Applied and Basic Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Zucoloto
Sérgio
S
da Fonseca
Benedito Antônio Lopes
BA
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
D016207:Cytokines; D012333:RNA, Messenger; D012367:RNA, Viral