This book, the proceedings of Falk Symposium No. 125 on
'Cytokines in Liver Injury and Repair' (Progress in
Gastroenterology and Hepatology Part II), held in Hannover,
Germany, on September 30 - October 1, 2001, provides an update of
our current knowledge on the role of cytokines in various human and
experimental liver diseases and on their present and prospective
use in therapeutic trials.
Developments in recent years include: Since the first report of
a cytokine knockout mouse for IL-2 in 1991 a large number of
cytokine and cytokine receptor genes have been inactivated in mouse
germlines and the corresponding mutant mice have provided a wealth
of novel information. In addition, targeted-gene disruption
techniques (e.g. cre-loxP) and liver-specific overexpression of
certain cytokines have provided clues for the understanding of
their role in the pathophysiology of liver diseases.
The number of well-characterized cytokines, chemokines, and
growth factors is ever growing and it becomes increasingly evident
that they are effective in a complex network of positive and
negative signals. A disruption of this homeostatic balance is a
direct cause of disease, determines its complications, and is
related to its progression, e.g. in inflammation and
fibrogenesis.
Signaling pathways from receptors to target genes have been
dissected and now we are beginning to recognize highly complicated
cross-talks between various signal transduction pathways and
interferences with non-cytokine mediators such as reactive oxygen
metabolites (ROS), lipid mediators, physical factors, and others
leading to an almost incomprehensible vastness of agonistic and
antagonistic signals.
Today, we understand in greater detail the extracellular control
mechanisms of cytokine and growth factor bioavailability and its
importance for pathophysiological mechanisms. During these
processes the secretion of (latent) proforms of cytokines, their
extracellular or transmembraneous immobilization and sustained
proteolytic activation and their release into the immediate
environment of cells play major roles and the possibility of
autocrine, paracrine, juxtacrine, and endocrine signal
transfer.
Finally, experimental and beginning clinical uses of proteins or
gene transfer technologies for cytokine antagonism, scavenging,
receptor blockade, and inhibition of signal cascades in therapeutic
trials offer hopeful perspectives in the treatment of malign and
benign liver diseases. Gene-therapeutic application of
molecular-engineered 'designer cytokines', e.g. of hyper-IL-6,
promises clinical benefit for the treatment of fulminant hepatic
failure.
The book contains chapters by most well-known experts in the
field who have contributed significantly to our present knowledge
on cytokines in liver injury and repair.
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