The effect of lipopolysaccharide (LPS) on the in vivo lethal action of doxorubicin (DOX) against mice was studied. DOX killed LPS-pretreated mice much earlier than untreated mice, and exhibited a stronger toxic action against LPS-pretreated mice. DOX-induced lethality in LPS-pretreated mice was due to severe hepatic damage, but there were no significant lesions in the heart, kidney and lung. Hepatic lesions were accompanied by caspase 3-positive cells and fragmented DNA-positive cells, suggesting the involvement of apoptosis. DOX induced the production of a high level of interferon (IFN)-γ and tumour necrosis factor (TNF)-α in LPS-pretreated mice, but not in non-treated mice. The DOX-induced lethality was prevented significantly by anti-IFN-γ antibody, but not anti-TNF-α antibody. Administration of recombinant IFN-γ in place of LPS augmented definitively the DOX-induced lethality. LPS augmented the DOX-induced lethality in TNF-α-deficient mice. Taken together, LPS was suggested to enhance DOX-induced IFN-γ production and augment the in vivo lethal action via hepatic damage.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy