Interleukin-2-induced hepatic injury involves temporal patterns of
cell adhesion in the microcirculation.
Lentsch, Alex B., Frederick N. Miller, Michael J. Edwards.
The Center for Applied Microcirculatory Research and the
Departments of Physiology and Biophysics, and [cedilla]cSurgery,
University of Louisville, Louisville, Kentucky, 40292
APStracts 3:0247G, 1996.
The treatment of metastatic cancer with interleukin-2 (IL-2) is
limited by systemic toxicities, including hepatic dysfunction. The
objective of this study was to determine the cellular mechanisms of
IL-2-induced hepatic injury. Intravital microscopy was used for the
direct observation of the murine hepatic microcirculation after 2
hours, 2 days, and 4 days of IL-2 treatment. At each interval,
leukocyte- and platelet-endothelial adherence were observed and
quantitated. Simultaneously, sinusoidal perfusion, serum levels of
glutamate pyruvate transaminase (SGPT), and edema were measured as
indices of hepatic toxicity. Acutely, IL-2 increased neutrophil
adhesion in association with decreased sinusoidal perfusion.
Leukocyte adhesion subsided at 2 days, but platelet-endothelial
interactions were enhanced and 40% of mice receiving IL-2 had
microvascular thrombi. These effects occurred in conjunction with
decreased sinusoidal perfusion and the development of hepatic edema.
After 4 days of IL-2, maximal hepatic edema, hypoperfusion, and
increased SGPT were associated with increased lymphocyte adhesion and
microvascular thrombosis. These data suggest coordinated, temporal
roles of leukocytes and platelets in the generation of IL-2-induced
hepatic injury.
Received 23 August 1996; accepted in final form 21 October 1996.
APS Manuscript Number G346-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996