AJP - Regulatory, Integrative and Comparative Physiology, Vol 268, Issue 3 699-R706, Copyright © 1995 by American Physiological Society
Role of corticosterone in TNF and IL-6 production in isolated perfused rat liver
J. Liao, J. A. Keiser, W. E. Scales, S. L. Kunkel and M. J. Kluger
Institute for Basic and Applied Medical Research, Lovelace Institutes, Albuquerque, New Mexico 87108.
Using an isolated perfused rat liver (IPRL) preparation, we assessed
whether corticosterone may contribute to the rise in tumor necrosis factor
(TNF) and interleukin-6 (IL-6) in rats after injection with
lipopolysaccharide (LPS) or exposure to psychological stress. Intravenous
infusion of LPS into the IPRL led to dose-dependent increases in TNF and
IL-6 concentrations in the effluent. Anisomycin, a protein synthesis
inhibitor, completely blocked the rise in TNF and IL-6 concentration in the
IPRL effluent, supporting the hypothesis that the synthesis (or release) of
these cytokines was dependent on protein synthesis. Intravenous infusion of
corticosterone at nonstressed (35 ng/ml) and stressed levels (350 ng/ml)
increased TNF and/or IL-6 release. However, when LPS was combined with
corticosterone, the lower dose of corticosterone facilitated the release of
cytokines, whereas the higher dose of corticosterone suppressed the release
of cytokines. We then showed that isolated Kupffer cells were capable of
significant TNF and IL-6 production and that corticosterone decreased
LPS-induced cytokine production in these cells. Our data support the
hypothesis that the liver is an important source of circulating cytokines
in response to LPS. In addition, although in vitro data generally support
the hypothesis that corticosterone suppresses the production of cytokines,
our in situ data support the hypothesis that physiological levels of
corticosterone cause an increase in TNF and IL-6.
