ISSN:
1420-908X
Keywords:
Key words: Endotoxin – Liver injury – Delayed-type hypersensitivity – Interferon-γ– TNF-α
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract: Objective and Design: To investigate the role of endotoxin in the development of immunologically induced liver injury.¶Materials and Methods: A new model of liver injury induced in BALB/c mice by delayed-type hypersensitivity to picryl chloride and its in vitro assay for the interaction between liver nonparenchymal and parenchymal cells were used.¶Results: Plasma endotoxin in the injured liver correlated well with serum alanine transaminase (ALT) activity (r = 0.601). Tolerance to lipopolysaccharide led to a significant inhibition of serum ALT elevation. However, lipopolysaccharide in vitro increased the ALT release from hepatocytes caused by nonparenchymal cells only in the presence of IFN-γ. When nonparenchymal cells were separated into Kupffer and non-Kupffer cell populations, the synergistic hepatotoxicity of lipopolysaccharide and IFN-γ was still observed in the former but not in the latter cell type. Lipopolysaccharide with IFN-γ also enhanced TNF-α levels. Anti-TNF-α almost completely inhibited the ALT release. Combined use of TNF-α and IFN-γ caused marked hepatocyte damage, while these cytokines alone did not.¶Conclusions: We suggest that elevated endotoxin levels accompanying the development of liver injury may activate Kupffer cells to release TNF-α leading to exacerbation of hepatocyte damage in cooperation with IFN-γ produced during liver injury.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s000110050633
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