Flavivirus infection as
dengue and
yellow fever persists as a terrible menace to pandemics, due to Aedes prevalence in the Americas.
Yellow fever is characterized by hepatocyte damage, with steatosis, apoptosis and
necrosis, mainly in the midzonal region of the liver, but the injury mechanism has not been studied at the light of recent knowledge, such as the advances in cell death mechanisms, inflammatory response and
cytokine cell expression tools. We studied 53 human liver
paraffin embedded blocks from patients who died with
yellow fever, all with histological demonstration of higher prevalence of apoptosis over
necrosis and mild disproportionate inflammatory response.
Viral antigens were found most frequently in hepatocytes from the midzonal area than other lobule areas, as detected by specific immunohistochemistry. Infiltrating cell subpopulations showed mainly CD4+ T lymphocytes, with small numbers of CD8+ cytotoxic lymphocytes, CD20+ B lymphocytes, NKT+ cells and S100+ dendritic cells in the sites of
inflammation, as compared to normal and
leptospirosis liver blocks. Some cells expressed
TNF-alpha and IFN-gamma, but a much more intense proportion of
TGF-beta expressing cells were found, suggesting both a Th1 and Th3 patterns of immune response in
yellow fever. Most affected hepatocyte presented apoptosis markers that appear at the cell death main pathway in this
infection.
Viral antigens, which production could interfere in hepatocyte biology, could induce the activation of apoptosis cascade, but
TGF-beta was also an apoptosis promoter. Our finding supports the key effect of the yellow fever virus in hepatocyte injury, resulting in prevalence of apoptosis over
necrosis, aside from a
TGF-beta action induced by the inflammatory response.