Related Experiment Videos
Mechanisms of interleukin-2-induced hepatic toxicity
K Nakagawa1, F N Miller, D E Sims
1Department of Surgery, University of Louisville, Kentucky 40292, USA.
Cancer Research
|February 1, 1996
Summary
Interleukin 2 (IL-2) causes liver damage by activating Kupffer cells, leading to reduced blood flow and hepatic dysfunction. This study reveals IL-2
Area of Science:
- Immunology
- Hepatology
- Oncology
Background:
- Interleukin 2 (IL-2) is used to treat metastatic cancer.
- Clinical use of IL-2 is limited by toxicities, including hepatic dysfunction.
- The mechanism of IL-2-induced liver injury is not fully understood.
Purpose of the Study:
- To investigate the mechanism of IL-2-induced hepatic dysfunction.
- To determine if IL-2 activates Kupffer cells, causing leukocyte adhesion and reduced hepatic blood flow.
Main Methods:
- C57BL/6 mice were treated with IL-2 and latex particles.
- Intravital hepatic microscopy assessed Kupffer cell activity, leukocyte-endothelial adhesion, and sinusoidal blood flow.
- Liver tissue was analyzed for TNF mRNA expression and by light/electron microscopy.
Main Results:
- IL-2 significantly increased Kupffer cell activity and leukocyte-endothelial adhesion.
- IL-2 significantly decreased sinusoidal blood flow.
- IL-2 induced TNF mRNA expression and caused sinusoidal constriction and hypoxic changes in the liver.
Conclusions:
- IL-2 activates Kupffer cells, leading to monokine release (including TNF).
- This activation causes leukocyte and platelet adhesion, impeding microcirculation.
- The resulting hepatic ischemia explains IL-2-induced liver dysfunction.