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.

There has been a tremendous amount of scientific progress in our understanding of the molecular mechanisms of transport processes in the liver within the last few years. Cloning of various members of organic anion and cation transporters has provided the necessary tools to study their regulation under physiological and pathophysiological conditions and has advanced our knowledge about bile formation. Mutations of various hepatic organic anion transporters have been identified in humans as hereditary defects leading to the heterogenous syndrome of progressive familial intrahepatic cholestasis (PFIC). Various mouse models including knockout animals have given us the opportunity to gain insight into lipid transport by the liver and the genetics of cholesterol gallstone formation. The physiology of bile duct cells and the molecular mechanisms leading to various cholangiopathies have been a main scientific focus in hepatology in recent years. Drug targeting to the liver by hepatic organic anion transporters represents an attractive way of selective delivery of pharmaceutical agents in humans. Ursodeoxycholic acid is successfully used in the treatment of patients with chronic cholestatic liver disease and major advances have been made in understanding its mode of action in liver and bile duct cells. This book, the proceedings of the Falk Workshop held in Aachen, Germany, on 25-26 January 2001, contains chapters on all important aspects of biliary transport by well-known experts in this field. It is an essential resource for new developments in the field of biliary transport, both in basic science and clinical medicine.

The last decade has seen tremendous developments in many fields of gastroenterology and hepatology. The aim of this series is to highlight some of these topics that deserve particular interest. Research in the field of viral hepatitis has been very intense and successful in recent years. The hepatitis B virus is one of the best explored at the current level of virology. Not only the nucleotid sequence of the viral DNA can be decoded, but also the amino acid compounds of its genetic products are known today. Since the techniques of molecular biology have increasingly found access to clinical laboratory use, hepatitis B virus infection can serve as an example for the importance of molecular biology in clinical hepa tology. Another example for the interdependence of basic science and clini cal medicine represents the research on bile acid metabolism. The investigation of bile acids has revealed new diagnostic approaches to hepatic and intestinal disorders. Commercial kits for the routine measurement of serum bile acids in clinical laboratories by enzymatic or radioimmunologic techniques are now available. The diagnostic value of these measurements in gastroenterology and hepatology shall be defined. Another aspect of bile acid research leads to new per spectives in the treatment of gallstone disease. The dissolution of cholesterol gallstones by chenodeoxycholic acid (therapy) may be quoted as the best example for the development of new phar macotherapeutic principles derived from basic bile acid research."

Inflammatory bowel disease - i.e. ulcerative colitis and Crohn's disease - not only creates significant patient morbidity but also imposes a diagnostic and therapeutic challenge to the physician in charge of these patients. Since the development of sulphasalazine by Dr Nanna Svartz in Sweden half a century ago, important improvements in the prognosis of ulcerative colitis and Crohn's disease have been achieved. This book makes an attempt to present and discuss some of the most recent advances in diagnostic procedures and therapeutic approaches to inflammatory bowel disease with special respect to Crohn's disease. Although the fmal diagnosis of ulcerative colitis and Crohn's disease is generally based on endoscopic, histological or X-ray examinations, nuclear medicine and its imaging procedures have established their place in certain aspects of inflammatory bowel disease. One chapter of this book is dedicated accordingly to the indications of nuclear diagnostic procedures in the clinical setting. Sulphasalazine has been the mainstay of medical therapy in ulcerative colitis and Crohn's disease of the colon. Recently 5-aminosalicylic acid has been discovered to be its active compound and sulphapyridine was found to be the component responsible for most of the adverse effects of sulpha salazine. It is not surprising that many studies have investigated 5-amino salicylic acid as a single therapeutic agent in inflammatory bowel disease."